Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

Background: Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease. Methods: Using test ( n =26) and validation ( n =18) cohorts, analysis of mutations, DNA methylation and transcr...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	British journal of cancer Ročník 117; číslo 2; s. 203 - 209
Hlavní autoři:	Alvi, Muhammad A, Loughrey, Maurice B, Dunne, Philip, McQuaid, Stephen, Turkington, Richard, Fuchs, Marc-Aurel, McGready, Claire, Bingham, Victoria, Pang, Brendan, Moore, Wendy, Maxwell, Perry, Lawler, Mark, James, Jacqueline A, Murray, Graeme I, Wilson, Richard H, Salto-Tellez, Manuel
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 11.07.2017 Nature Publishing Group
Témata:	631/208/727 692/4028/67/1059/2325 692/4028/67/1059/602 692/4028/67/1504/1885 Adaptive immunity Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Signet Ring Cell - genetics Carcinoma, Signet Ring Cell - pathology CD3 antigen Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology CpG islands CpG Islands - genetics DNA methylation DNA Methylation - genetics Drug Resistance Epidemiology Female Gene expression Gene Expression Regulation, Neoplastic Genomics Genotype Genotypes Humans Immune checkpoint inhibitors Immunohistochemistry Lymphoid cells Male Microsatellite Instability Molecular Medicine Mutation Neoplasm Proteins - biosynthesis Oncology Precision medicine Proto-Oncogene Proteins B-raf - genetics Statistical analysis Transcriptome - genetics Translational Therapeutics PDL1 KIT genotype
ISSN:	0007-0920, 1532-1827, 1532-1827
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Abstract	Background: Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease. Methods: Using test ( n =26) and validation ( n =18) cohorts, analysis of mutations, DNA methylation and transcriptome was carried out. Microsatellite instability (MSI) status was established and immunohistochemistry (IHC) was used to test for adaptive immunity (CD3) and the immune checkpoint PDL1. Results: DNA methylation data split the cohorts into hypermethylated ( n =18, 41%) and hypomethylated groups ( n =26, 59%). The hypermethylated group predominant in the proximal colon was enriched for CpG island methylator phenotype (CIMP), BRAF V600E mutation and MSI ( P <0.001). These cases also had a high CD3 + immune infiltrate ( P <0.001) and expressed PDL1 ( P =0.03 in intra-tumoural lymphoid cells). The hypomethylated group predominant in the distal colon did not show any characteristic molecular features. We also detected a common targetable KIT mutation (c.1621A>C) across both groups. No statistically significant difference in outcome was observed between the two groups. Conclusions: Our data show that SRCCa phenotype comprises two distinct genotypes. The MSI + /CIMP + / BRAF V600E + /CD3 + /PDL1 + hypermethylated genotype is an ideal candidate for immune checkpoint inhibitor therapy. In addition, one fourth of SRCCa cases can potentially be targeted by KIT inhibitors.
AbstractList	Background:Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease.Methods:Using test (n=26) and validation (n=18) cohorts, analysis of mutations, DNA methylation and transcriptome was carried out. Microsatellite instability (MSI) status was established and immunohistochemistry (IHC) was used to test for adaptive immunity (CD3) and the immune checkpoint PDL1.Results:DNA methylation data split the cohorts into hypermethylated (n=18, 41%) and hypomethylated groups (n=26, 59%). The hypermethylated group predominant in the proximal colon was enriched for CpG island methylator phenotype (CIMP), BRAF V600E mutation and MSI (P<0.001). These cases also had a high CD3+ immune infiltrate (P<0.001) and expressed PDL1 (P=0.03 in intra-tumoural lymphoid cells). The hypomethylated group predominant in the distal colon did not show any characteristic molecular features. We also detected a common targetable KIT mutation (c.1621A>C) across both groups. No statistically significant difference in outcome was observed between the two groups.Conclusions:Our data show that SRCCa phenotype comprises two distinct genotypes. The MSI+ /CIMP+ /BRAF V600E+ /CD3+ /PDL1+ hypermethylated genotype is an ideal candidate for immune checkpoint inhibitor therapy. In addition, one fourth of SRCCa cases can potentially be targeted by KIT inhibitors. Background: Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease. Methods: Using test ( n =26) and validation ( n =18) cohorts, analysis of mutations, DNA methylation and transcriptome was carried out. Microsatellite instability (MSI) status was established and immunohistochemistry (IHC) was used to test for adaptive immunity (CD3) and the immune checkpoint PDL1. Results: DNA methylation data split the cohorts into hypermethylated ( n =18, 41%) and hypomethylated groups ( n =26, 59%). The hypermethylated group predominant in the proximal colon was enriched for CpG island methylator phenotype (CIMP), BRAF V600E mutation and MSI ( P <0.001). These cases also had a high CD3 + immune infiltrate ( P <0.001) and expressed PDL1 ( P =0.03 in intra-tumoural lymphoid cells). The hypomethylated group predominant in the distal colon did not show any characteristic molecular features. We also detected a common targetable KIT mutation (c.1621A>C) across both groups. No statistically significant difference in outcome was observed between the two groups. Conclusions: Our data show that SRCCa phenotype comprises two distinct genotypes. The MSI + /CIMP + / BRAF V600E + /CD3 + /PDL1 + hypermethylated genotype is an ideal candidate for immune checkpoint inhibitor therapy. In addition, one fourth of SRCCa cases can potentially be targeted by KIT inhibitors. Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease.BACKGROUNDSignet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease.Using test (n=26) and validation (n=18) cohorts, analysis of mutations, DNA methylation and transcriptome was carried out. Microsatellite instability (MSI) status was established and immunohistochemistry (IHC) was used to test for adaptive immunity (CD3) and the immune checkpoint PDL1.METHODSUsing test (n=26) and validation (n=18) cohorts, analysis of mutations, DNA methylation and transcriptome was carried out. Microsatellite instability (MSI) status was established and immunohistochemistry (IHC) was used to test for adaptive immunity (CD3) and the immune checkpoint PDL1.DNA methylation data split the cohorts into hypermethylated (n=18, 41%) and hypomethylated groups (n=26, 59%). The hypermethylated group predominant in the proximal colon was enriched for CpG island methylator phenotype (CIMP), BRAF V600E mutation and MSI (P<0.001). These cases also had a high CD3+ immune infiltrate (P<0.001) and expressed PDL1 (P=0.03 in intra-tumoural lymphoid cells). The hypomethylated group predominant in the distal colon did not show any characteristic molecular features. We also detected a common targetable KIT mutation (c.1621A>C) across both groups. No statistically significant difference in outcome was observed between the two groups.RESULTSDNA methylation data split the cohorts into hypermethylated (n=18, 41%) and hypomethylated groups (n=26, 59%). The hypermethylated group predominant in the proximal colon was enriched for CpG island methylator phenotype (CIMP), BRAF V600E mutation and MSI (P<0.001). These cases also had a high CD3+ immune infiltrate (P<0.001) and expressed PDL1 (P=0.03 in intra-tumoural lymphoid cells). The hypomethylated group predominant in the distal colon did not show any characteristic molecular features. We also detected a common targetable KIT mutation (c.1621A>C) across both groups. No statistically significant difference in outcome was observed between the two groups.Our data show that SRCCa phenotype comprises two distinct genotypes. The MSI+/CIMP+/BRAF V600E+/CD3+/PDL1+ hypermethylated genotype is an ideal candidate for immune checkpoint inhibitor therapy. In addition, one fourth of SRCCa cases can potentially be targeted by KIT inhibitors.CONCLUSIONSOur data show that SRCCa phenotype comprises two distinct genotypes. The MSI+/CIMP+/BRAF V600E+/CD3+/PDL1+ hypermethylated genotype is an ideal candidate for immune checkpoint inhibitor therapy. In addition, one fourth of SRCCa cases can potentially be targeted by KIT inhibitors. Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease. Using test (n=26) and validation (n=18) cohorts, analysis of mutations, DNA methylation and transcriptome was carried out. Microsatellite instability (MSI) status was established and immunohistochemistry (IHC) was used to test for adaptive immunity (CD3) and the immune checkpoint PDL1. DNA methylation data split the cohorts into hypermethylated (n=18, 41%) and hypomethylated groups (n=26, 59%). The hypermethylated group predominant in the proximal colon was enriched for CpG island methylator phenotype (CIMP), BRAF V600E mutation and MSI (P<0.001). These cases also had a high CD3 immune infiltrate (P<0.001) and expressed PDL1 (P=0.03 in intra-tumoural lymphoid cells). The hypomethylated group predominant in the distal colon did not show any characteristic molecular features. We also detected a common targetable KIT mutation (c.1621A>C) across both groups. No statistically significant difference in outcome was observed between the two groups. Our data show that SRCCa phenotype comprises two distinct genotypes. The MSI /CIMP /BRAF V600E /CD3 /PDL1 hypermethylated genotype is an ideal candidate for immune checkpoint inhibitor therapy. In addition, one fourth of SRCCa cases can potentially be targeted by KIT inhibitors.
Author	Loughrey, Maurice B McGready, Claire Alvi, Muhammad A Fuchs, Marc-Aurel Wilson, Richard H Moore, Wendy Dunne, Philip Salto-Tellez, Manuel Bingham, Victoria Maxwell, Perry McQuaid, Stephen Pang, Brendan Lawler, Mark Turkington, Richard James, Jacqueline A Murray, Graeme I
Author_xml	– sequence: 1 givenname: Muhammad A surname: Alvi fullname: Alvi, Muhammad A organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 2 givenname: Maurice B surname: Loughrey fullname: Loughrey, Maurice B organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Department of Histopathology, Royal Victoria Hospital, Belfast Health and Social Care Trust – sequence: 3 givenname: Philip surname: Dunne fullname: Dunne, Philip organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 4 givenname: Stephen surname: McQuaid fullname: McQuaid, Stephen organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 5 givenname: Richard surname: Turkington fullname: Turkington, Richard organization: Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 6 givenname: Marc-Aurel surname: Fuchs fullname: Fuchs, Marc-Aurel organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 7 givenname: Claire surname: McGready fullname: McGready, Claire organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 8 givenname: Victoria surname: Bingham fullname: Bingham, Victoria organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 9 givenname: Brendan surname: Pang fullname: Pang, Brendan organization: Department of Pathology, National University Hospital, National University Health System – sequence: 10 givenname: Wendy surname: Moore fullname: Moore, Wendy organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 11 givenname: Perry surname: Maxwell fullname: Maxwell, Perry organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 12 givenname: Mark surname: Lawler fullname: Lawler, Mark organization: Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 13 givenname: Jacqueline A surname: James fullname: James, Jacqueline A organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 14 givenname: Graeme I surname: Murray fullname: Murray, Graeme I organization: Department of Pathology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen – sequence: 15 givenname: Richard H surname: Wilson fullname: Wilson, Richard H organization: Centre for Cancer Research and Cell Biology, Queen’s University Belfast – sequence: 16 givenname: Manuel surname: Salto-Tellez fullname: Salto-Tellez, Manuel email: m.salto-tellez@qub.ac.uk organization: Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Department of Histopathology, Royal Victoria Hospital, Belfast Health and Social Care Trust
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/28595259$$D View this record in MEDLINE/PubMed
BookMark	eNp1kktv1DAUhS1URKeFHWtkiQ0LMviROPEGqap4SUVsYG15nJuMB8cOtlOJ_8EPxum0qFSwsq_83aPrc88ZOvHBA0LPKdlSwrs3u4PZMkLbLRXdI7ShDWcV7Vh7gjaEkLYikpFTdJbSoZSSdO0TdMq6RjaskRv063NwYBanI55jGKyzfsRhwMmOHjKOa2nAOWyCCxFM1uWqvYEb_tr2kLDGKcdQwKizDV47wEOIeAQfJmtw1nGEDD3Wvsd2mhYP2OzBfJ-D9Rlbv7c7m0tD3kPUs4X0FD0etEvw7PY8R9_ev_t6-bG6-vLh0-XFVWUaKnLFJTSko4JK2Rqmu3YQUtZ8pwUlNQEme65FN4CpuRB8oJoKRpgZelm-DpLxc_T2qDsvuwl6Az5H7dQc7aTjTxW0VX-_eLtXY7hWTcNIQ9si8OpWIIYfC6SsJptWu7SHsCRFi98156wVBX35AD2EJRazVoq2UtSibgr14v5Ef0a5W1gB2BEwMaQUYVDG5hvby4DWKUrUmgpVUqHWVKiSitL0-kHTne5_8OqIp3ndP8R7o_6L_w3BeMqp
CitedBy_id	crossref_primary_10_1007_s10637_023_01403_1 crossref_primary_10_1186_s12957_024_03362_0 crossref_primary_10_1016_j_heliyon_2024_e34220 crossref_primary_10_26599_AGR_2025_9340049 crossref_primary_10_1016_j_tranon_2018_04_007 crossref_primary_10_1002_iju5_12462 crossref_primary_10_1038_s41598_024_73952_1 crossref_primary_10_1186_s12876_022_02175_3 crossref_primary_10_3389_pore_2021_1609859 crossref_primary_10_3390_cancers15092497 crossref_primary_10_1016_j_ctarc_2021_100475 crossref_primary_10_1186_s12876_019_1083_0 crossref_primary_10_1016_j_tranon_2018_07_008 crossref_primary_10_3390_medsci6020031 crossref_primary_10_1038_s41388_024_03029_w crossref_primary_10_3389_fmolb_2021_706754 crossref_primary_10_1038_s12276_020_0373_5 crossref_primary_10_1136_jcp_2023_208816 crossref_primary_10_1158_1078_0432_CCR_18_3388 crossref_primary_10_3390_cancers15082288 crossref_primary_10_1016_j_pathol_2020_10_010 crossref_primary_10_1038_bjc_2017_321 crossref_primary_10_1016_j_ajpath_2018_08_015 crossref_primary_10_1177_1758835919856494 crossref_primary_10_1186_s12885_019_6144_9 crossref_primary_10_1016_j_cmpb_2024_108193 crossref_primary_10_3390_cancers11071036 crossref_primary_10_1002_jso_25044 crossref_primary_10_3390_cancers12061544 crossref_primary_10_3390_jcm9010286 crossref_primary_10_12998_wjcc_v8_i4_658 crossref_primary_10_1007_s00432_020_03410_8 crossref_primary_10_1038_s41388_022_02350_6 crossref_primary_10_2217_fon_2020_0242 crossref_primary_10_1186_s13000_020_01019_6 crossref_primary_10_4251_wjgo_v16_i5_2141 crossref_primary_10_1016_j_bbcan_2022_188722 crossref_primary_10_1007_s00384_020_03707_7 crossref_primary_10_4103_aja202186
Cites_doi	10.1073/pnas.96.15.8681 10.1093/jnci/djj137 10.1186/s12885-015-1925-2 10.1007/s00384-010-1037-z 10.18632/oncotarget.7343 10.1038/nm.3967 10.1158/2159-8290.CD-14-1397 10.1038/nature15393 10.1038/nature19057 10.1097/SLA.0b013e3182a69f7e 10.1007/BF02305663 10.1371/journal.pone.0069604 10.1158/2159-8290.CD-14-0863 10.1038/modpathol.2012.44 10.1007/978-3-540-46091-6_12 10.1038/nature14011 10.1056/NEJMoa1500596 10.1038/nrclinonc.2009.237 10.18632/oncotarget.4576 10.1136/gutjnl-2015-310912 10.1126/science.aac9935 10.1158/0008-5472.CAN-14-3362
ContentType	Journal Article
Copyright	The Author(s) 2017 Copyright Nature Publishing Group Jul 11, 2017 Copyright © 2017 The Author(s) 2017 The Author(s)
Copyright_xml	– notice: The Author(s) 2017 – notice: Copyright Nature Publishing Group Jul 11, 2017 – notice: Copyright © 2017 The Author(s) 2017 The Author(s)
DBID	C6C AAYXX CITATION CGR CUY CVF ECM EIF NPM 3V. 7RV 7TO 7U9 7X7 7XB 88E 8AO 8C1 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AN0 AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ H94 HCIFZ K9. KB0 LK8 M0S M1P M7P NAPCQ PHGZM PHGZT PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS 7X8 5PM
DOI	10.1038/bjc.2017.168
DatabaseName	Springer Nature OA Free Journals CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed ProQuest Central (Corporate) Nursing & Allied Health Database Oncogenes and Growth Factors Abstracts Virology and AIDS Abstracts Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) ProQuest Pharma Collection Public Health Database (ProQuest) ProQuest SciTech Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland British Nursing Database ProQuest Central Essentials - QC Biological Science Collection ProQuest Central Natural Science Collection ProQuest One ProQuest Central Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student AIDS and Cancer Research Abstracts SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Database (Alumni Edition) Biological Sciences ProQuest Health & Medical Collection PML(ProQuest Medical Library) Biological Science Database Nursing & Allied Health Premium ProQuest Central Premium ProQuest One Academic ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) One Applied & Life Sciences ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China MEDLINE - Academic PubMed Central (Full Participant titles)
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) ProQuest Central Student Oncogenes and Growth Factors Abstracts ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Central China ProQuest Central ProQuest One Applied & Life Sciences ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Health & Medical Research Collection Biological Science Collection AIDS and Cancer Research Abstracts ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Public Health Virology and AIDS Abstracts ProQuest Biological Science Collection ProQuest One Academic Eastern Edition British Nursing Index with Full Text ProQuest Nursing & Allied Health Source ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection ProQuest Hospital Collection (Alumni) Nursing & Allied Health Premium ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest Nursing & Allied Health Source (Alumni) ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic
DatabaseTitleList	ProQuest Central Student MEDLINE - Academic MEDLINE
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7RV name: Nursing & Allied Health Database url: https://search.proquest.com/nahs sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Medicine
DocumentTitleAlternate	Molecular profiling of signet ring cell cancer
EISSN	1532-1827
EndPage	209
ExternalDocumentID	PMC5520517 28595259 10_1038_bjc_2017_168
Genre	Journal Article
GrantInformation_xml	– fundername: Cancer Research UK grantid: 20256
GroupedDBID	--- -Q- 0R~ 23N 36B 39C 3V. 4.4 406 53G 5GY 5RE 6J9 70F 7RV 7X7 88E 8AO 8C1 8FI 8FJ 8R4 8R5 AACDK AANZL AASML AATNV AAWTL AAYZH AAZLF ABAKF ABLJU ABOCM ABUWG ABZZP ACAOD ACGFO ACGFS ACKTT ACPRK ACRQY ACZOJ ADBBV ADFRT ADHDB AEFQL AEJRE AEMSY AENEX AEVLU AEXYK AFBBN AFKRA AFRAH AFSHS AGAYW AGHAI AGQEE AHMBA AHSBF AIGIU AILAN AJRNO ALFFA ALMA_UNASSIGNED_HOLDINGS AMYLF AN0 AOIJS ASPBG AVWKF AXYYD AZFZN BAWUL BBNVY BENPR BHPHI BKEYQ BKKNO BNQBC BPHCQ BVXVI C6C CCPQU CS3 DIK DNIVK DPUIP DU5 E3Z EAP EBLON EBS EE. EIOEI EJD EMB ESX EX3 F5P FDQFY FEDTE FERAY FIGPU FIZPM FRJ FSGXE FYUFA GX1 HCIFZ HMCUK HVGLF HYE HZ~ IH2 IWAJR JSO JZLTJ KQ8 M1P M7P NAO NAPCQ NQJWS O9- OK1 P2P PQQKQ PROAC PSQYO Q2X RNT RNTTT ROL RPM SNX SNYQT SOHCF SOJ SRMVM SWTZT TAOOD TBHMF TDRGL TR2 UKHRP W2D WH7 WOW ~02 AAFWJ AAYXX ABBRH ABDBE ABFSG ABRTQ ACSTC AEZWR AFDZB AFFHD AFHIU AHWEU AIXLP ATHPR AYFIA CITATION PHGZM PHGZT PJZUB PPXIY PQGLB CGR CUY CVF ECM EIF NPM 7TO 7U9 7XB 8FE 8FH 8FK AZQEC DWQXO GNUQQ H94 K9. LK8 PKEHL PQEST PQUKI PRINS 7X8 PUEGO 5PM
ID	FETCH-LOGICAL-c516t-39e508161997c2a87f69943ba61040e29d3a68fec43663f1a16202cfd9259e923
IEDL.DBID	7RV
ISICitedReferencesCount	43
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000405189700012&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	0007-0920 1532-1827
IngestDate	Tue Nov 04 01:50:44 EST 2025 Thu Sep 04 17:18:59 EDT 2025 Tue Oct 07 05:13:08 EDT 2025 Mon Jul 21 05:50:34 EDT 2025 Tue Nov 18 21:00:26 EST 2025 Sat Nov 29 02:47:25 EST 2025 Fri Feb 21 02:39:42 EST 2025
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	2
Keywords	PDL1 KIT genotype
Language	English
License	This work is licensed under the Creative Commons Attribution-Non-Commercial-Share Alike 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c516t-39e508161997c2a87f69943ba61040e29d3a68fec43663f1a16202cfd9259e923
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
OpenAccessLink	https://pubmed.ncbi.nlm.nih.gov/PMC5520517
PMID	28595259
PQID	1917964645
PQPubID	41855
PageCount	7
ParticipantIDs	pubmedcentral_primary_oai_pubmedcentral_nih_gov_5520517 proquest_miscellaneous_1908433276 proquest_journals_1917964645 pubmed_primary_28595259 crossref_citationtrail_10_1038_bjc_2017_168 crossref_primary_10_1038_bjc_2017_168 springer_journals_10_1038_bjc_2017_168
PublicationCentury	2000
PublicationDate	2017-07-11
PublicationDateYYYYMMDD	2017-07-11
PublicationDate_xml	– month: 07 year: 2017 text: 2017-07-11 day: 11
PublicationDecade	2010
PublicationPlace	London
PublicationPlace_xml	– name: London – name: England
PublicationTitle	British journal of cancer
PublicationTitleAbbrev	Br J Cancer
PublicationTitleAlternate	Br J Cancer
PublicationYear	2017
Publisher	Nature Publishing Group UK Nature Publishing Group
Publisher_xml	– name: Nature Publishing Group UK – name: Nature Publishing Group
References	Le, Uram, Wang, Bartlett, Kemberling, Eyring, Skora, Luber, Azad, Laheru, Biedrzycki, Donehower, Zaheer, Fisher, Crocenzi, Lee, Duffy, Goldberg, de la Chapelle, Koshiji, Bhaijee, Huebner, Hruban, Wood, Cuka, Pardoll, Papadopoulos, Kinzler, Zhou, Cornish, Taube, Anders, Eshleman, Vogelstein, Diaz (CR16) 2015; 372 Siehl, Thiel (CR22) 2007; 176 Kane, Loda, Gaida, Lipman, Mishra, Goldman, Jessup, Kolodner (CR14) 1997; 57 Arnold, Sierra, Laversanne, Soerjomataram, Jemal, Bray (CR3) 2017; 66 Barras (CR4) 2015; 7 (CR23) 2015; 526 Masago, Fujita, Muraki, Hata, Okuda, Otsuka, Kaji, Takeshita, Kato, Katakami, Hirata (CR19) 2015; 15 Toyota, Ahuja, Ohe-Toyota, Herman, Baylin, Issa (CR24) 1999; 96 Anthony, George, Rodriguez-Bigas, Petrelli (CR2) 1996; 3 Vilar, Gruber (CR25) 2010; 7 Alvi, McArt, Kelly, Fuchs, Alderdice, McCabe, Bingham, McGready, Tripathi, Emmert-Streib, Loughrey, McQuaid, Maxwell, Hamilton, Turkington, James, Wilson, Salto-Tellez (CR1) 2015; 6 Casey, Tong, Li, Do, Walz, Fitzgerald, Gouw, Baylot, Guetegemann, Eilers, Felsher (CR6) 2016; 352 CR5 Kakar, Deng, Smyrk, Cun, Sahai, Kim (CR13) 2012; 25 Lastwika, Wilson, Li, Norris, Xu, Ghazarian, Kitagawa, Kawabata, Taube, Yao, Liu, Gills, Dennis (CR15) 2016; 76 Nitsche, Zimmermann, Späth, Müller, Maak, Schuster, Slotta-Huspenina, Käser, Michalski, Janssen, Friess, Rosenberg, Bader (CR21) 2013; 258 CR7 Gopalan, Smith, Ho, Lam (CR9) 2011; 26 Gonçalves, Monges, Yang, Palmerini, Dubreuil, Noguchi, Jacquemier, Di Stefano, Delpero, Sobol, Bertucci (CR8) 2006; 98 Llosa, Cruise, Tam, Wicks, Hechenbleikner, Taube, Blosser, Fan, Wang, Luber, Zhang, Papadopoulos, Kinzler, Vogelstein, Sears, Anders, Pardoll, Housseau (CR18) 2015; 5 Iacono, Buttigliero, Monica, Bollito, Garrou, Cappia, Rapa, Vignani, Bertaglia, Fiori, Papotti, Volante, Scagliotti, Porpiglia, Tucci (CR12) 2016; 7 Guinney, Dienstmann, Wang, de Reynies, Schlicker, Soneson, Marisa, Roepman, Nyamundanda, Angelino, Bot, Morris, Simon, Gerster, Fessler, De Sousa, Missiaglia, Ramay, Barras, Homicsko, Maru, Manyam, Broom, Boige, Perez-Villamil, Laderas, Salazar, Gray, Hanahan, Tabernero, Bernards, Friend, Laurent-Puig, Medema, Sadanandam, Wessels, Delorenzi, Kopetz, Vermeulen, Tejpar (CR10) 2015; 21 Xiao, Freeman (CR26) 2015; 5 Herbst, Soria, Kowanetz, Fine, Hamid, Gordon, Sosman, McDermott, Powderly, Gettinger, Kohrt, Horn, Lawrence, Rost, Leabman, Xiao, Mokatrin, Koeppen, Hegde, Mellman, Chen, Hodi (CR11) 2014; 515 McCourt, McArt, Mills, Catherwood, Maxwell, Waugh, Hamilton, O’Sullivan, Salto-Tellez (CR20) 2013; 8 Lek, Karczewski, Minikel, Samocha, Banks, Fennell, O'Donnell-Luria, Ware, Hill, Cummings, Tukiainen, Birnbaum, Kosmicki, Duncan, Estrada, Zhao, Zou, Pierce-Hoffman, Cooper, DePristo, Do, Flannick, Fromer, Gauthier, Goldstein, Gupta, Howrigan, Kiezun, Kurki, Levy Moonshine, Natarajan, Orozco, Peloso, Poplin, Rivas, Ruano-Rubio, Ruderfer, Shakir, Stenson, Stevens, Thomas, Tiao, Tusie-Luna, Weisburd, Won, Yu, Altshuler, Ardissino, Boehnke, Danesh, Roberto, Florez, Gabriel, Getz, Hultman, Kathiresan, Laakso, McCarroll, McCarthy, McGovern, McPherson, Neale, Palotie, Purcell, Saleheen, Scharf, Sklar, Patrick, Tuomilehto, Watkins, Wilson, Daly, MacArthur (CR17) 2016; 536 Y Xiao (BFbjc2017168_CR26) 2015; 5 DT Le (BFbjc2017168_CR16) 2015; 372 E Vilar (BFbjc2017168_CR25) 2010; 7 MA Alvi (BFbjc2017168_CR1) 2015; 6 D Barras (BFbjc2017168_CR4) 2015; 7 V Gopalan (BFbjc2017168_CR9) 2011; 26 M Arnold (BFbjc2017168_CR3) 2017; 66 U Nitsche (BFbjc2017168_CR21) 2013; 258 SC Casey (BFbjc2017168_CR6) 2016; 352 BFbjc2017168_CR7 M Lek (BFbjc2017168_CR17) 2016; 536 T Anthony (BFbjc2017168_CR2) 1996; 3 ML Iacono (BFbjc2017168_CR12) 2016; 7 BFbjc2017168_CR5 K Masago (BFbjc2017168_CR19) 2015; 15 KJ Lastwika (BFbjc2017168_CR15) 2016; 76 CM McCourt (BFbjc2017168_CR20) 2013; 8 A Gonçalves (BFbjc2017168_CR8) 2006; 98 J Guinney (BFbjc2017168_CR10) 2015; 21 M Toyota (BFbjc2017168_CR24) 1999; 96 RS Herbst (BFbjc2017168_CR11) 2014; 515 MF Kane (BFbjc2017168_CR14) 1997; 57 The Genomes Project C (BFbjc2017168_CR23) 2015; 526 S Kakar (BFbjc2017168_CR13) 2012; 25 NJ Llosa (BFbjc2017168_CR18) 2015; 5 J Siehl (BFbjc2017168_CR22) 2007; 176
References_xml	– volume: 96 start-page: 8681 issue: 15 year: 1999 end-page: 8686 ident: CR24 article-title: CpG island methylator phenotype in colorectal cancer publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.96.15.8681 – volume: 98 start-page: 562 issue: 8 year: 2006 end-page: 563 ident: CR8 article-title: Response of a KIT-positive extra-abdominal fibromatosis to imatinib mesylate and KIT genetic analysis publication-title: J Natl Cancer Inst doi: 10.1093/jnci/djj137 – volume: 15 start-page: 1 issue: 1 year: 2015 end-page: 8 ident: CR19 article-title: Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations publication-title: BMC Cancer doi: 10.1186/s12885-015-1925-2 – volume: 26 start-page: 127 issue: 2 year: 2011 end-page: 133 ident: CR9 article-title: Signet-ring cell carcinoma of colorectum–current perspectives and molecular biology publication-title: Int J Colorectal Dis doi: 10.1007/s00384-010-1037-z – volume: 7 start-page: 14394 year: 2016 end-page: 14404 ident: CR12 article-title: Retrospective study testing next generation sequencing of selected cancer-associated genes in resected prostate cancer publication-title: Oncotarget doi: 10.18632/oncotarget.7343 – volume: 21 start-page: 1350 issue: 11 year: 2015 end-page: 1356 ident: CR10 article-title: The consensus molecular subtypes of colorectal cancer publication-title: Nat Med doi: 10.1038/nm.3967 – volume: 57 start-page: 808 issue: 5 year: 1997 end-page: 811 ident: CR14 article-title: Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines publication-title: Cancer Res – volume: 5 start-page: 16 issue: 1 year: 2015 end-page: 18 ident: CR26 article-title: The Microsatellite Instable (MSI) subset of colorectal cancer is a particularly good candidate for checkpoint blockade immunotherapy publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-14-1397 – volume: 526 start-page: 68 issue: 7571 year: 2015 end-page: 74 ident: CR23 article-title: A global reference for human genetic variation publication-title: Nature doi: 10.1038/nature15393 – volume: 536 start-page: 285 issue: 7616 year: 2016 end-page: 291 ident: CR17 article-title: Analysis of protein-coding genetic variation in 60,706 humans publication-title: Nature doi: 10.1038/nature19057 – volume: 258 start-page: 775 issue: 5 year: 2013 end-page: 782 ident: CR21 article-title: Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis publication-title: Ann Surg doi: 10.1097/SLA.0b013e3182a69f7e – volume: 3 start-page: 344 issue: 4 year: 1996 end-page: 348 ident: CR2 article-title: Primary signet-ring cell carcinoma of the colon and rectum publication-title: Ann Surg Oncol doi: 10.1007/BF02305663 – volume: 8 start-page: e69604 issue: 7 year: 2013 ident: CR20 article-title: Validation of next generation sequencing technologies in comparison to current diagnostic gold standards for BRAF, EGFR and KRAS mutational analysis publication-title: PLoS ONE doi: 10.1371/journal.pone.0069604 – volume: 5 start-page: 43 issue: 1 year: 2015 end-page: 51 ident: CR18 article-title: The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-14-0863 – volume: 25 start-page: 1040 issue: 7 year: 2012 end-page: 1047 ident: CR13 article-title: Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma publication-title: Mod Pathol doi: 10.1038/modpathol.2012.44 – volume: 176 start-page: 145 year: 2007 end-page: 151 ident: CR22 article-title: C-kit, GIST, and imatinib publication-title: Recent Results Cancer Res doi: 10.1007/978-3-540-46091-6_12 – volume: 515 start-page: 563 issue: 7528 year: 2014 end-page: 567 ident: CR11 article-title: Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients publication-title: Nature doi: 10.1038/nature14011 – volume: 372 start-page: 2509 issue: 26 year: 2015 end-page: 2520 ident: CR16 article-title: PD-1 blockade in tumors with mismatch-repair deficiency publication-title: N Engl J Med doi: 10.1056/NEJMoa1500596 – volume: 7 start-page: 153 issue: 3 year: 2010 end-page: 162 ident: CR25 article-title: Microsatellite instability in colorectal cancer-the stable evidence publication-title: Nat Rev Clin Oncol doi: 10.1038/nrclinonc.2009.237 – ident: CR5 – ident: CR7 – volume: 6 start-page: 20863 issue: 25 year: 2015 end-page: 20874 ident: CR1 article-title: Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility publication-title: Oncotarget doi: 10.18632/oncotarget.4576 – volume: 66 start-page: 683 issue: 4 year: 2017 end-page: 691 ident: CR3 article-title: Global patterns and trends in colorectal cancer incidence and mortality publication-title: Gut doi: 10.1136/gutjnl-2015-310912 – volume: 352 start-page: 227 issue: Suppl 1 year: 2016 end-page: 231 ident: CR6 article-title: MYC regulates the antitumor immune response through CD47 and PD-L1 publication-title: Science doi: 10.1126/science.aac9935 – volume: 7 start-page: 9 issue: Suppl 1 year: 2015 end-page: 12 ident: CR4 article-title: BRAF mutation in colorectal cancer: an update publication-title: Biomark Cancer – volume: 76 start-page: 227 issue: 2 year: 2016 end-page: 238 ident: CR15 article-title: Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-14-3362 – volume: 176 start-page: 145 year: 2007 ident: BFbjc2017168_CR22 publication-title: Recent Results Cancer Res doi: 10.1007/978-3-540-46091-6_12 – volume: 25 start-page: 1040 issue: 7 year: 2012 ident: BFbjc2017168_CR13 publication-title: Mod Pathol doi: 10.1038/modpathol.2012.44 – volume: 5 start-page: 16 issue: 1 year: 2015 ident: BFbjc2017168_CR26 publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-14-1397 – ident: BFbjc2017168_CR7 – volume: 15 start-page: 1 issue: 1 year: 2015 ident: BFbjc2017168_CR19 publication-title: BMC Cancer doi: 10.1186/s12885-015-1925-2 – ident: BFbjc2017168_CR5 – volume: 5 start-page: 43 issue: 1 year: 2015 ident: BFbjc2017168_CR18 publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-14-0863 – volume: 258 start-page: 775 issue: 5 year: 2013 ident: BFbjc2017168_CR21 publication-title: Ann Surg doi: 10.1097/SLA.0b013e3182a69f7e – volume: 6 start-page: 20863 issue: 25 year: 2015 ident: BFbjc2017168_CR1 publication-title: Oncotarget doi: 10.18632/oncotarget.4576 – volume: 7 start-page: 153 issue: 3 year: 2010 ident: BFbjc2017168_CR25 publication-title: Nat Rev Clin Oncol doi: 10.1038/nrclinonc.2009.237 – volume: 66 start-page: 683 issue: 4 year: 2017 ident: BFbjc2017168_CR3 publication-title: Gut doi: 10.1136/gutjnl-2015-310912 – volume: 352 start-page: 227 issue: Suppl 1 year: 2016 ident: BFbjc2017168_CR6 publication-title: Science doi: 10.1126/science.aac9935 – volume: 536 start-page: 285 issue: 7616 year: 2016 ident: BFbjc2017168_CR17 publication-title: Nature doi: 10.1038/nature19057 – volume: 8 start-page: e69604 issue: 7 year: 2013 ident: BFbjc2017168_CR20 publication-title: PLoS ONE doi: 10.1371/journal.pone.0069604 – volume: 3 start-page: 344 issue: 4 year: 1996 ident: BFbjc2017168_CR2 publication-title: Ann Surg Oncol doi: 10.1007/BF02305663 – volume: 57 start-page: 808 issue: 5 year: 1997 ident: BFbjc2017168_CR14 publication-title: Cancer Res – volume: 76 start-page: 227 issue: 2 year: 2016 ident: BFbjc2017168_CR15 publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-14-3362 – volume: 98 start-page: 562 issue: 8 year: 2006 ident: BFbjc2017168_CR8 publication-title: J Natl Cancer Inst doi: 10.1093/jnci/djj137 – volume: 515 start-page: 563 issue: 7528 year: 2014 ident: BFbjc2017168_CR11 publication-title: Nature doi: 10.1038/nature14011 – volume: 7 start-page: 9 issue: Suppl 1 year: 2015 ident: BFbjc2017168_CR4 publication-title: Biomark Cancer – volume: 7 start-page: 14394 year: 2016 ident: BFbjc2017168_CR12 publication-title: Oncotarget doi: 10.18632/oncotarget.7343 – volume: 96 start-page: 8681 issue: 15 year: 1999 ident: BFbjc2017168_CR24 publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.96.15.8681 – volume: 526 start-page: 68 issue: 7571 year: 2015 ident: BFbjc2017168_CR23 publication-title: Nature doi: 10.1038/nature15393 – volume: 372 start-page: 2509 issue: 26 year: 2015 ident: BFbjc2017168_CR16 publication-title: N Engl J Med doi: 10.1056/NEJMoa1500596 – volume: 21 start-page: 1350 issue: 11 year: 2015 ident: BFbjc2017168_CR10 publication-title: Nat Med doi: 10.1038/nm.3967 – volume: 26 start-page: 127 issue: 2 year: 2011 ident: BFbjc2017168_CR9 publication-title: Int J Colorectal Dis doi: 10.1007/s00384-010-1037-z
SSID	ssj0009087
Score	2.4236326
Snippet	Background: Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of... Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine... Background:Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of...
SourceID	pubmedcentral proquest pubmed crossref springer
SourceType	Open Access Repository Aggregation Database Index Database Enrichment Source Publisher
StartPage	203
SubjectTerms	631/208/727 692/4028/67/1059/2325 692/4028/67/1059/602 692/4028/67/1504/1885 Adaptive immunity Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Signet Ring Cell - genetics Carcinoma, Signet Ring Cell - pathology CD3 antigen Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology CpG islands CpG Islands - genetics DNA methylation DNA Methylation - genetics Drug Resistance Epidemiology Female Gene expression Gene Expression Regulation, Neoplastic Genomics Genotype Genotypes Humans Immune checkpoint inhibitors Immunohistochemistry Lymphoid cells Male Microsatellite Instability Molecular Medicine Mutation Neoplasm Proteins - biosynthesis Oncology Precision medicine Proto-Oncogene Proteins B-raf - genetics Statistical analysis Transcriptome - genetics Translational Therapeutics
Title	Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies
URI	https://link.springer.com/article/10.1038/bjc.2017.168 https://www.ncbi.nlm.nih.gov/pubmed/28595259 https://www.proquest.com/docview/1917964645 https://www.proquest.com/docview/1908433276 https://pubmed.ncbi.nlm.nih.gov/PMC5520517
Volume	117
WOSCitedRecordID	wos000405189700012&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVPQU databaseName: Biological Science Database customDbUrl: eissn: 1532-1827 dateEnd: 20171231 omitProxy: false ssIdentifier: ssj0009087 issn: 0007-0920 databaseCode: M7P dateStart: 20000101 isFulltext: true titleUrlDefault: http://search.proquest.com/biologicalscijournals providerName: ProQuest – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1532-1827 dateEnd: 20171231 omitProxy: false ssIdentifier: ssj0009087 issn: 0007-0920 databaseCode: 7X7 dateStart: 20000101 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: Nursing & Allied Health Database customDbUrl: eissn: 1532-1827 dateEnd: 20171231 omitProxy: false ssIdentifier: ssj0009087 issn: 0007-0920 databaseCode: 7RV dateStart: 20000101 isFulltext: true titleUrlDefault: https://search.proquest.com/nahs providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: eissn: 1532-1827 dateEnd: 20171231 omitProxy: false ssIdentifier: ssj0009087 issn: 0007-0920 databaseCode: BENPR dateStart: 20000101 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVPQU databaseName: Public Health Database customDbUrl: eissn: 1532-1827 dateEnd: 20171231 omitProxy: false ssIdentifier: ssj0009087 issn: 0007-0920 databaseCode: 8C1 dateStart: 20000101 isFulltext: true titleUrlDefault: https://search.proquest.com/publichealth providerName: ProQuest
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Lb9QwEB5BixAX3o9AWQ0ScEFRE-dlnxBUrbh0taoA7S1yHKcNj2TZpPwSfjAzibNlKXDhYkXKKHEy4_G8_A3Ac6GySsSF8mk1leygZL4md9mvMsa3U0qUqhqaTWTzuVwu1cIF3DpXVjnpxEFRl63hGPk--xUq5Tzc69U3n7tGcXbVtdC4Crsh790kz9nJxwvQ3UCOmJkcjlMicIXvQST3i0-MXxhydEVub0mX7MzL5ZK_5UyHrejo1v9-xG246YxQfDNKzR24Ypu7cP3YpdnvwY_jqWkujj29aRrYVsjFHrZHnhVyxB8Z8ppVJj3MsPgM9Hyyr0ONHUfZT3Htwo0WyT5GxoT9WhscK9BtibopseZDKhZJfsznVVs3PdbNWV2QslnjeECM_Pn78OHo8P3BO9-1b_BNEqa9HymbcFsPLmUxQsusSpWKo0KTxRYHVqgy0qmsrIkjMnuqUIepCISpSkUumSXD8wHsNG1jHwEGiS3jWFhSzDouQ1PQtY6kjSp6ZhEID15NHMyNwzbnFhtf8iHHHsmc-J0zv3PitwcvNtSrEdPjL3R7Exdzt7K7_IKFHjzb3KY1yb9dN7Y9Z5pAMi5clnrwcJSdzYsYMDChD_Qg25KqDQHjfW_faeqzAfc7SQQjqnnwcpK_X6b1h_k__vf8n8ANpuRAdRjuwU6_PrdP4Zr53tfdejasJB6X2TBKGuVBOIPdt4fzxcmMi2QXPwGtNC64
linkProvider	ProQuest
linkToHtml	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwEB5VBQEX3oVAgUGiXFDUxHk4PiCEgKpVuysORdpbcByHhkeybFIQ_4PfwW9kJo8tS4FbD9wiZTZxvN-MPQ9_A_BIKFmIMFMuaVPODop0NbnLbiGZ304pkauiazYhp9NkNlOv1-DHeBaGyypHm9gZ6rw2HCPfZr9CxZyHezb_7HLXKM6uji00eljs229fyWVrnu69pP93S4idV4cvdt2hq4BrIj9u3UDZiLtNcIWFETqRRaxUGGSaNhKhZ4XKAx0nhTVhQKtx4Ws_Fp4wRa7IU7CKiQ7I5J8jOy65hEzO5AnJr5f0HJ0c_lPCGwrtvSDZzt4zX6LP0ZxkdQk8ta89XZ75W462W_p2rvxvk3YVLg-bbHzea8U1WLPVdbgwGcoIbsD3ydgUGPue5fTZWBfIxSy2RZ4F5IwGMqU3Lwn0MMPq0cnzycUGNTacRXiHiyGcapH2_8ict59Kg32Fvc1RVzmWfAjHIumH-TCvy6rFsjoqMzKmC-wPwJW2uQlvzmRONmC9qit7G9CLbB6GwtLCo8PcNxld6yCxQUHPzDzhwJMRMakZuNu5hcjHtKshCJKU8JUyvlLClwNbS-l5z1nyF7nNETXpYLma9AQyDjxc3iabw9OuK1sfs4yXMO-djB241WN1-SImRIzoAx2QKyheCjCf-eqdqjzqeM2jSDBjnAOPR7z_Mqw_jP_Ov8f_AC7uHk4O0oO96f5duMS_4qC872_Cers4tvfgvPnSls3ifqfFCG_PWgN-AiHpguM
linkToPdf	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9RADLaqFlVceD8CBYxEuaBok8lzDggB7YqqdLVCIPUWJpMZGh7JstmC-B_8Gn4ddh5blgK3HrhFijeZzH62xx7PZ4AHQiZWhLl0SZsKDlASV1G47NqE-e2kFIW0bbOJZDJJDw_ldA1-DGdhuKxysImtoS5qzTnyEccVMuZ9uJHtyyKmO-Mns88ud5DindahnUYHkX3z7SuFb83jvR36r7eFGO--fv7C7TsMuDry44UbSBNx5wmuttBCpYmNpQyDXNGiIvSMkEWg4tQaHQbkma2v_Fh4QttCUtRgJJMekPnfSGiRQdq18Wx3Mn11QvnrpR1jJycDpfD6snsvSEf5e2ZP9Dm3k646xFOr3NPFmr_t2LaOcHzxf57CS3ChX37j005fLsOaqa7A5kFfYHAVvh8M7YKx62ZOU4C1RS5zMQvkGUHe60Am-2ZnQQ_TrDitPJ9pbFBhw_sL73DeJ1oNUmSAzIb7qdTY1d6bAlVVYMnHcwyS5ugPs7qsFlhWR2VOZnaO3dG40jTX4M2ZzMl1WK_qytwE9CJThKEw5JJUWPg6p2sVpCaw9MzcEw48GtCT6Z7VnZuLfMza6oIgzQhrGWMtI6w5sL2UnnVsJn-R2xoQlPU2rclO4OPA_eVtskY87aoy9THLeCkz4iWxAzc63C5fxFSJEX2gA8kKopcCzHS-eqcqj1rG8ygSzCXnwMMB-78M6w_jv_Xv8d-DTQJ-9nJvsn8bzvOPOFvv-1uwvpgfmztwTn9ZlM38bq_SCG_PWgV-AqBkjQQ
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Molecular+profiling+of+signet+ring+cell+colorectal+cancer+provides+a+strong+rationale+for+genomic+targeted+and+immune+checkpoint+inhibitor+therapies&rft.jtitle=British+journal+of+cancer&rft.au=Alvi%2C+Muhammad+A&rft.au=Loughrey%2C+Maurice+B&rft.au=Dunne%2C+Philip&rft.au=McQuaid%2C+Stephen&rft.date=2017-07-11&rft.pub=Nature+Publishing+Group&rft.issn=0007-0920&rft.eissn=1532-1827&rft.volume=117&rft.issue=2&rft.spage=203&rft.epage=209&rft_id=info:doi/10.1038%2Fbjc.2017.168&rft_id=info%3Apmid%2F28595259&rft.externalDocID=PMC5520517
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0007-0920&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0007-0920&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0007-0920&client=summon