Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer
Microsatellite instability (MSI) and/or mismatch repair deficiency (MMR-D) testing has traditionally been performed in patients with colorectal (CRC) and endometrial cancer (EC) to screen for Lynch syndrome (LS)-associated cancer predisposition. The recent success of immunotherapy in high-frequency...
Uloženo v:
| Vydáno v: | Journal of clinical oncology Ročník 37; číslo 4; s. 286 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
01.02.2019
|
| Témata: | |
| ISSN: | 1527-7755, 1527-7755 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | Microsatellite instability (MSI) and/or mismatch repair deficiency (MMR-D) testing has traditionally been performed in patients with colorectal (CRC) and endometrial cancer (EC) to screen for Lynch syndrome (LS)-associated cancer predisposition. The recent success of immunotherapy in high-frequency MSI (MSI-H) and/or MMR-D tumors now supports testing for MSI in all advanced solid tumors. The extent to which LS accounts for MSI-H across heterogeneous tumor types is unknown. Here, we establish the prevalence of LS across solid tumors according to MSI status.
MSI status was determined using targeted next-generation sequencing, with tumors classified as MSI-H, MSI-indeterminate, or microsatellite-stable. Matched germline DNA was analyzed for mutations in LS-associated mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, EPCAM). In patients with LS with MSI-H/I tumors, immunohistochemical staining for MMR-D was assessed.
Among 15,045 unique patients (more than 50 cancer types), LS was identified in 16.3% (53 of 326), 1.9% (13 of 699), and 0.3% (37 of 14,020) of patients with MSI-H, MSI-indeterminate, and microsatellite-stable tumors, respectively ( P < .001). Among patients with LS with MSI-H/I tumors, 50% (33 of 66) had tumors other than CRC/EC, including urothelial, prostate, pancreas, adrenocortical, small bowel, sarcoma, mesothelioma, melanoma, gastric, and germ cell tumors. In these patients with non-CRC/EC tumors, 45% (15 of 33) did not meet LS genetic testing criteria on the basis of personal/family history. Immunohistochemical staining of LS-positive MSI-H/I tumors demonstrated MMR-D in 98.2% (56 of 57) of available cases.
MSI-H/MMR-D is predictive of LS across a much broader tumor spectrum than currently appreciated. Given implications for cancer surveillance and prevention measures in affected families, these data support germline genetic assessment for LS for patients with an MSI-H/MMR-D tumor, regardless of cancer type or family cancer history. |
|---|---|
| AbstractList | Microsatellite instability (MSI) and/or mismatch repair deficiency (MMR-D) testing has traditionally been performed in patients with colorectal (CRC) and endometrial cancer (EC) to screen for Lynch syndrome (LS)-associated cancer predisposition. The recent success of immunotherapy in high-frequency MSI (MSI-H) and/or MMR-D tumors now supports testing for MSI in all advanced solid tumors. The extent to which LS accounts for MSI-H across heterogeneous tumor types is unknown. Here, we establish the prevalence of LS across solid tumors according to MSI status.PURPOSEMicrosatellite instability (MSI) and/or mismatch repair deficiency (MMR-D) testing has traditionally been performed in patients with colorectal (CRC) and endometrial cancer (EC) to screen for Lynch syndrome (LS)-associated cancer predisposition. The recent success of immunotherapy in high-frequency MSI (MSI-H) and/or MMR-D tumors now supports testing for MSI in all advanced solid tumors. The extent to which LS accounts for MSI-H across heterogeneous tumor types is unknown. Here, we establish the prevalence of LS across solid tumors according to MSI status.MSI status was determined using targeted next-generation sequencing, with tumors classified as MSI-H, MSI-indeterminate, or microsatellite-stable. Matched germline DNA was analyzed for mutations in LS-associated mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, EPCAM). In patients with LS with MSI-H/I tumors, immunohistochemical staining for MMR-D was assessed.METHODSMSI status was determined using targeted next-generation sequencing, with tumors classified as MSI-H, MSI-indeterminate, or microsatellite-stable. Matched germline DNA was analyzed for mutations in LS-associated mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, EPCAM). In patients with LS with MSI-H/I tumors, immunohistochemical staining for MMR-D was assessed.Among 15,045 unique patients (more than 50 cancer types), LS was identified in 16.3% (53 of 326), 1.9% (13 of 699), and 0.3% (37 of 14,020) of patients with MSI-H, MSI-indeterminate, and microsatellite-stable tumors, respectively ( P < .001). Among patients with LS with MSI-H/I tumors, 50% (33 of 66) had tumors other than CRC/EC, including urothelial, prostate, pancreas, adrenocortical, small bowel, sarcoma, mesothelioma, melanoma, gastric, and germ cell tumors. In these patients with non-CRC/EC tumors, 45% (15 of 33) did not meet LS genetic testing criteria on the basis of personal/family history. Immunohistochemical staining of LS-positive MSI-H/I tumors demonstrated MMR-D in 98.2% (56 of 57) of available cases.RESULTSAmong 15,045 unique patients (more than 50 cancer types), LS was identified in 16.3% (53 of 326), 1.9% (13 of 699), and 0.3% (37 of 14,020) of patients with MSI-H, MSI-indeterminate, and microsatellite-stable tumors, respectively ( P < .001). Among patients with LS with MSI-H/I tumors, 50% (33 of 66) had tumors other than CRC/EC, including urothelial, prostate, pancreas, adrenocortical, small bowel, sarcoma, mesothelioma, melanoma, gastric, and germ cell tumors. In these patients with non-CRC/EC tumors, 45% (15 of 33) did not meet LS genetic testing criteria on the basis of personal/family history. Immunohistochemical staining of LS-positive MSI-H/I tumors demonstrated MMR-D in 98.2% (56 of 57) of available cases.MSI-H/MMR-D is predictive of LS across a much broader tumor spectrum than currently appreciated. Given implications for cancer surveillance and prevention measures in affected families, these data support germline genetic assessment for LS for patients with an MSI-H/MMR-D tumor, regardless of cancer type or family cancer history.CONCLUSIONMSI-H/MMR-D is predictive of LS across a much broader tumor spectrum than currently appreciated. Given implications for cancer surveillance and prevention measures in affected families, these data support germline genetic assessment for LS for patients with an MSI-H/MMR-D tumor, regardless of cancer type or family cancer history. Microsatellite instability (MSI) and/or mismatch repair deficiency (MMR-D) testing has traditionally been performed in patients with colorectal (CRC) and endometrial cancer (EC) to screen for Lynch syndrome (LS)-associated cancer predisposition. The recent success of immunotherapy in high-frequency MSI (MSI-H) and/or MMR-D tumors now supports testing for MSI in all advanced solid tumors. The extent to which LS accounts for MSI-H across heterogeneous tumor types is unknown. Here, we establish the prevalence of LS across solid tumors according to MSI status. MSI status was determined using targeted next-generation sequencing, with tumors classified as MSI-H, MSI-indeterminate, or microsatellite-stable. Matched germline DNA was analyzed for mutations in LS-associated mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, EPCAM). In patients with LS with MSI-H/I tumors, immunohistochemical staining for MMR-D was assessed. Among 15,045 unique patients (more than 50 cancer types), LS was identified in 16.3% (53 of 326), 1.9% (13 of 699), and 0.3% (37 of 14,020) of patients with MSI-H, MSI-indeterminate, and microsatellite-stable tumors, respectively ( P < .001). Among patients with LS with MSI-H/I tumors, 50% (33 of 66) had tumors other than CRC/EC, including urothelial, prostate, pancreas, adrenocortical, small bowel, sarcoma, mesothelioma, melanoma, gastric, and germ cell tumors. In these patients with non-CRC/EC tumors, 45% (15 of 33) did not meet LS genetic testing criteria on the basis of personal/family history. Immunohistochemical staining of LS-positive MSI-H/I tumors demonstrated MMR-D in 98.2% (56 of 57) of available cases. MSI-H/MMR-D is predictive of LS across a much broader tumor spectrum than currently appreciated. Given implications for cancer surveillance and prevention measures in affected families, these data support germline genetic assessment for LS for patients with an MSI-H/MMR-D tumor, regardless of cancer type or family cancer history. |
| Author | Bandlamudi, Chaitanya Walsh, Michael F Zhang, Liying Shia, Jinru Solit, David B Latham, Alicia Saltz, Leonard B Galle, Jesse Penson, Alexander Offit, Kenneth Hechtman, Jaclyn Janjigian, Yelena Cadoo, Karen Hyman, David M O'Reilly, Eileen M Vijai, Joseph Zehir, Ahmet Segal, Neil Robson, Mark E Reidy-Lagunes, Diane Varghese, Anna M Taylor, Barry S Tran, Christina Stewart, Carolyn Srinivasan, Preethi Baselga, Jose Weiser, Martin Berger, Michael F Aguilar, Julio Garcia Ladanyi, Marc Sheehan, Margaret Kemel, Yelena Bajorin, Dean Middha, Sumit Mandelker, Diana Carlo, Maria I Yaeger, Rona Dickson, Mark A Klimstra, David S Dubard-Gault, Marianne Diaz, Jr, Luis A DeLair, Deborah Mukherjee, Semanti Stadler, Zsofia K |
| Author_xml | – sequence: 1 givenname: Alicia surname: Latham fullname: Latham, Alicia organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 2 givenname: Preethi surname: Srinivasan fullname: Srinivasan, Preethi organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 3 givenname: Yelena surname: Kemel fullname: Kemel, Yelena organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 4 givenname: Jinru surname: Shia fullname: Shia, Jinru organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 5 givenname: Chaitanya surname: Bandlamudi fullname: Bandlamudi, Chaitanya organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 6 givenname: Diana surname: Mandelker fullname: Mandelker, Diana organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 7 givenname: Sumit surname: Middha fullname: Middha, Sumit organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 8 givenname: Jaclyn surname: Hechtman fullname: Hechtman, Jaclyn organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 9 givenname: Ahmet surname: Zehir fullname: Zehir, Ahmet organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 10 givenname: Marianne surname: Dubard-Gault fullname: Dubard-Gault, Marianne organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 11 givenname: Christina surname: Tran fullname: Tran, Christina organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 12 givenname: Carolyn surname: Stewart fullname: Stewart, Carolyn organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 13 givenname: Margaret surname: Sheehan fullname: Sheehan, Margaret organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 14 givenname: Alexander surname: Penson fullname: Penson, Alexander organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 15 givenname: Deborah surname: DeLair fullname: DeLair, Deborah organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 16 givenname: Rona surname: Yaeger fullname: Yaeger, Rona organization: 2 Weill Cornell Medical College, New York, NY – sequence: 17 givenname: Joseph surname: Vijai fullname: Vijai, Joseph organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 18 givenname: Semanti surname: Mukherjee fullname: Mukherjee, Semanti organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 19 givenname: Jesse surname: Galle fullname: Galle, Jesse organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 20 givenname: Mark A surname: Dickson fullname: Dickson, Mark A organization: 2 Weill Cornell Medical College, New York, NY – sequence: 21 givenname: Yelena surname: Janjigian fullname: Janjigian, Yelena organization: 2 Weill Cornell Medical College, New York, NY – sequence: 22 givenname: Eileen M surname: O'Reilly fullname: O'Reilly, Eileen M organization: 2 Weill Cornell Medical College, New York, NY – sequence: 23 givenname: Neil surname: Segal fullname: Segal, Neil organization: 2 Weill Cornell Medical College, New York, NY – sequence: 24 givenname: Leonard B surname: Saltz fullname: Saltz, Leonard B organization: 2 Weill Cornell Medical College, New York, NY – sequence: 25 givenname: Diane surname: Reidy-Lagunes fullname: Reidy-Lagunes, Diane organization: 2 Weill Cornell Medical College, New York, NY – sequence: 26 givenname: Anna M surname: Varghese fullname: Varghese, Anna M organization: 2 Weill Cornell Medical College, New York, NY – sequence: 27 givenname: Dean surname: Bajorin fullname: Bajorin, Dean organization: 2 Weill Cornell Medical College, New York, NY – sequence: 28 givenname: Maria I surname: Carlo fullname: Carlo, Maria I organization: 2 Weill Cornell Medical College, New York, NY – sequence: 29 givenname: Karen surname: Cadoo fullname: Cadoo, Karen organization: 2 Weill Cornell Medical College, New York, NY – sequence: 30 givenname: Michael F surname: Walsh fullname: Walsh, Michael F organization: 2 Weill Cornell Medical College, New York, NY – sequence: 31 givenname: Martin surname: Weiser fullname: Weiser, Martin organization: 2 Weill Cornell Medical College, New York, NY – sequence: 32 givenname: Julio Garcia surname: Aguilar fullname: Aguilar, Julio Garcia organization: 2 Weill Cornell Medical College, New York, NY – sequence: 33 givenname: David S surname: Klimstra fullname: Klimstra, David S organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 34 givenname: Luis A surname: Diaz, Jr fullname: Diaz, Jr, Luis A organization: 2 Weill Cornell Medical College, New York, NY – sequence: 35 givenname: Jose surname: Baselga fullname: Baselga, Jose organization: 2 Weill Cornell Medical College, New York, NY – sequence: 36 givenname: Liying surname: Zhang fullname: Zhang, Liying organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 37 givenname: Marc surname: Ladanyi fullname: Ladanyi, Marc organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 38 givenname: David M surname: Hyman fullname: Hyman, David M organization: 2 Weill Cornell Medical College, New York, NY – sequence: 39 givenname: David B surname: Solit fullname: Solit, David B organization: 2 Weill Cornell Medical College, New York, NY – sequence: 40 givenname: Mark E surname: Robson fullname: Robson, Mark E organization: 2 Weill Cornell Medical College, New York, NY – sequence: 41 givenname: Barry S surname: Taylor fullname: Taylor, Barry S organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 42 givenname: Kenneth surname: Offit fullname: Offit, Kenneth organization: 1 Memorial Sloan Kettering Cancer Center, New York, NY – sequence: 43 givenname: Michael F surname: Berger fullname: Berger, Michael F organization: 2 Weill Cornell Medical College, New York, NY – sequence: 44 givenname: Zsofia K surname: Stadler fullname: Stadler, Zsofia K organization: 2 Weill Cornell Medical College, New York, NY |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30376427$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkE1LAzEYhINU7IfePEuOXrbmY7NJj2WxWqlUUOlxSbJvaKSbrZv0sP_eBSt4moFnGJiZolFoAyB0S8mcMkIeXsrtnKo5IUzxCzShgslMSiFG__wYTWP8IoTmiosrNOaEyyJncoJ2r952bdQJDgefAK9DTNr4wfd4HfEyxtb6gdZ459Mepz3gtw4iBAu4dXjTB7vH732ou7YZkA5ZqQfWXaNLpw8Rbs46Q5-rx4_yOdtsn9blcpNZrvKU5cyIYYQhOVeFI1YbyVTOHHFuYZgqJANaS7VwBmxB61wrYhwXikrKQRLFZuj-t_fYtd8niKlqfLTDGB2gPcWKUSYLsSgEGaJ35-jJNFBXx843uuurvzPYD903YUo |
| CitedBy_id | crossref_primary_10_1007_s00535_019_01620_7 crossref_primary_10_1016_j_amjsurg_2025_116393 crossref_primary_10_1007_s10689_024_00395_y crossref_primary_10_1038_s41467_022_30496_0 crossref_primary_10_1200_EDBK_321209 crossref_primary_10_18027_2224_5057_2023_13_3s1_40_48 crossref_primary_10_1056_NEJMc2036233 crossref_primary_10_5858_arpa_2021_0632_CP crossref_primary_10_1016_j_jpba_2023_115630 crossref_primary_10_1007_s11910_021_01149_4 crossref_primary_10_1002_kjm2_12926 crossref_primary_10_1146_annurev_med_052318_101009 crossref_primary_10_1053_j_gastro_2019_08_059 crossref_primary_10_1093_jjco_hyac183 crossref_primary_10_1016_j_chmed_2021_11_003 crossref_primary_10_1177_17588359211018539 crossref_primary_10_3389_fbioe_2022_850669 crossref_primary_10_1080_14737159_2020_1816170 crossref_primary_10_1007_s00384_021_03985_9 crossref_primary_10_3389_fimmu_2022_953421 crossref_primary_10_1111_his_14271 crossref_primary_10_1007_s41971_020_00085_3 crossref_primary_10_1038_s41698_025_01038_w crossref_primary_10_2217_fon_2021_0874 crossref_primary_10_3389_fonc_2023_1176950 crossref_primary_10_1097_CEJ_0000000000000787 crossref_primary_10_1002_ijc_33214 crossref_primary_10_1111_jog_15197 crossref_primary_10_1007_s00428_022_03358_9 crossref_primary_10_3390_cancers14184479 crossref_primary_10_3390_cancers15153833 crossref_primary_10_1111_his_15133 crossref_primary_10_1053_j_gastro_2021_06_073 crossref_primary_10_3390_cancers13030467 crossref_primary_10_1177_1758835919848189 crossref_primary_10_1016_j_cmpb_2022_107095 crossref_primary_10_1007_s10072_020_04987_1 crossref_primary_10_1016_j_it_2022_04_010 crossref_primary_10_1016_j_jtho_2023_05_028 crossref_primary_10_1093_jjco_hyad148 crossref_primary_10_3389_fonc_2023_1280022 crossref_primary_10_1016_j_dld_2021_03_011 crossref_primary_10_2217_bmm_2020_0674 crossref_primary_10_1016_j_ucl_2023_01_012 crossref_primary_10_3389_fonc_2022_832228 crossref_primary_10_1002_jcph_2340 crossref_primary_10_3389_fimmu_2022_926740 crossref_primary_10_1016_j_critrevonc_2021_103241 crossref_primary_10_3389_fimmu_2024_1425596 crossref_primary_10_1097_CEJ_0000000000000870 crossref_primary_10_1007_s12032_025_02849_4 crossref_primary_10_1002_mgg3_2506 crossref_primary_10_1016_j_ejca_2024_115142 crossref_primary_10_3390_diagnostics11030478 crossref_primary_10_1158_1078_0432_CCR_23_1807 crossref_primary_10_1111_jgh_15937 crossref_primary_10_1038_s41523_022_00490_2 crossref_primary_10_3389_fonc_2023_1193503 crossref_primary_10_1007_s00330_022_08954_6 crossref_primary_10_1093_jnci_djad063 crossref_primary_10_3390_diagnostics13111867 crossref_primary_10_1002_ijc_34312 crossref_primary_10_1136_gutjnl_2023_329492 crossref_primary_10_1186_s40792_023_01780_y crossref_primary_10_1016_j_pathol_2023_12_412 crossref_primary_10_3389_fimmu_2025_1628979 crossref_primary_10_1002_ijc_35085 crossref_primary_10_1093_clinchem_hvaa013 crossref_primary_10_3389_fonc_2023_1147591 crossref_primary_10_3390_cancers15113023 crossref_primary_10_1038_s41431_025_01913_x crossref_primary_10_1186_s12575_024_00238_1 crossref_primary_10_3390_cancers12071848 crossref_primary_10_3389_fcell_2022_876180 crossref_primary_10_1002_jhbp_1063 crossref_primary_10_1016_j_isci_2024_111073 crossref_primary_10_3390_cancers15072053 crossref_primary_10_1016_j_bpobgyn_2020_01_005 crossref_primary_10_1016_j_critrevonc_2024_104387 crossref_primary_10_1053_j_gastro_2021_04_010 crossref_primary_10_3389_fimmu_2024_1344272 crossref_primary_10_1016_j_ctarc_2020_100165 crossref_primary_10_1159_000520023 crossref_primary_10_1200_EDBK_398068 crossref_primary_10_1016_j_esmogo_2023_100037 crossref_primary_10_3390_cancers12113188 crossref_primary_10_1007_s12325_021_01956_8 crossref_primary_10_1016_j_critrevonc_2020_103171 crossref_primary_10_1038_s41417_023_00721_z crossref_primary_10_1200_JCO_18_01664 crossref_primary_10_3390_genes14111991 crossref_primary_10_1038_s41467_024_54970_z crossref_primary_10_3390_biomedicines13040773 crossref_primary_10_1002_iju5_70062 crossref_primary_10_1007_s40261_020_00915_5 crossref_primary_10_1007_s00292_021_00948_3 crossref_primary_10_1056_NEJMoa2017699 crossref_primary_10_1200_EDBK_240839 crossref_primary_10_20892_j_issn_2095_3941_2021_0585 crossref_primary_10_1016_j_urolonc_2022_07_016 crossref_primary_10_1016_j_prp_2024_155152 crossref_primary_10_1111_his_14228 crossref_primary_10_3390_ijms23158535 crossref_primary_10_1136_gutjnl_2020_320726 crossref_primary_10_1097_CCO_0000000000000525 crossref_primary_10_31083_j_fbl2902087 crossref_primary_10_1016_j_humpath_2021_05_009 crossref_primary_10_1007_s00053_024_00772_2 crossref_primary_10_1007_s40265_020_01304_0 crossref_primary_10_1016_j_jmoldx_2023_07_003 crossref_primary_10_1038_s41439_022_00185_x crossref_primary_10_3390_cells9092019 crossref_primary_10_1016_j_dnarep_2021_103176 crossref_primary_10_1016_j_esmogo_2024_100044 crossref_primary_10_1136_bmjonc_2024_000335 crossref_primary_10_1200_EDBK_279867 crossref_primary_10_3389_fonc_2020_00168 crossref_primary_10_1016_j_semcancer_2021_12_004 crossref_primary_10_1093_jjco_hyab175 crossref_primary_10_1245_s10434_020_08209_y crossref_primary_10_1016_j_hoc_2024_01_006 crossref_primary_10_1016_j_ygyno_2019_12_031 crossref_primary_10_1016_j_annonc_2023_05_010 crossref_primary_10_1007_s11938_022_00386_x crossref_primary_10_1007_s10147_023_02397_9 crossref_primary_10_1016_j_gim_2022_05_003 crossref_primary_10_1038_s41571_021_00492_2 crossref_primary_10_5858_arpa_2022_0418_OA crossref_primary_10_1007_s12029_020_00467_z crossref_primary_10_1111_jog_15273 crossref_primary_10_3390_biomedicines10051035 crossref_primary_10_1038_s41591_023_02544_9 crossref_primary_10_1177_10781552221094308 crossref_primary_10_1016_j_neo_2025_101207 crossref_primary_10_1136_gutjnl_2020_320730 crossref_primary_10_3389_fonc_2025_1563022 crossref_primary_10_1016_j_heliyon_2024_e34375 crossref_primary_10_3389_fimmu_2021_757804 crossref_primary_10_3389_fonc_2024_1329133 crossref_primary_10_1007_s13105_024_01033_y crossref_primary_10_3389_fonc_2021_682872 crossref_primary_10_3390_diagnostics11020199 crossref_primary_10_1038_s41392_024_01979_x crossref_primary_10_1038_s41598_024_58899_7 crossref_primary_10_1136_bmjopen_2024_091745 crossref_primary_10_1155_2021_5514426 crossref_primary_10_3389_fonc_2025_1485386 crossref_primary_10_3390_cancers12061676 crossref_primary_10_1016_j_modpat_2025_100769 crossref_primary_10_3389_fimmu_2023_1061761 crossref_primary_10_1053_j_gastro_2022_08_058 crossref_primary_10_1093_jnci_djad016 crossref_primary_10_1038_s41598_021_94292_4 crossref_primary_10_3390_cancers16112111 crossref_primary_10_1093_gastro_goab030 crossref_primary_10_1111_cas_15157 crossref_primary_10_1038_s41391_019_0153_2 crossref_primary_10_1186_s13073_022_01101_2 crossref_primary_10_3390_diagnostics11071195 crossref_primary_10_1016_j_urolonc_2019_12_012 crossref_primary_10_1134_S0026893323010041 crossref_primary_10_3892_ol_2024_14653 crossref_primary_10_2147_CEG_S278054 crossref_primary_10_1016_j_jgo_2020_01_001 crossref_primary_10_1097_PAS_0000000000002031 crossref_primary_10_1007_s43152_024_00054_5 crossref_primary_10_1186_s12885_022_09172_5 crossref_primary_10_3390_life12020229 crossref_primary_10_1002_pros_24711 crossref_primary_10_7717_peerj_15920 crossref_primary_10_1158_1078_0432_CCR_22_0713 crossref_primary_10_1038_s41698_025_00925_6 crossref_primary_10_1177_2050313X21999200 crossref_primary_10_1016_j_jmoldx_2021_10_011 crossref_primary_10_1210_clinem_dgaa833 crossref_primary_10_1016_j_ejca_2024_115196 crossref_primary_10_1002_cam4_71080 crossref_primary_10_3389_fimmu_2020_02039 crossref_primary_10_3390_cells14100745 crossref_primary_10_1016_j_ygyno_2022_12_008 crossref_primary_10_1186_s12885_024_12843_0 crossref_primary_10_1016_j_jss_2024_10_041 crossref_primary_10_1055_a_2258_8565 crossref_primary_10_1016_j_clgc_2024_01_011 crossref_primary_10_1038_s41568_024_00744_0 crossref_primary_10_1097_XCS_0000000000000134 crossref_primary_10_1038_s41571_025_01015_z crossref_primary_10_1007_s00795_022_00324_x crossref_primary_10_1016_j_ebiom_2022_104120 crossref_primary_10_1016_j_soi_2024_100091 crossref_primary_10_1007_s10120_024_01523_4 crossref_primary_10_1038_s41598_020_73421_5 crossref_primary_10_1158_1078_0432_CCR_20_2892 crossref_primary_10_1007_s13691_020_00457_9 crossref_primary_10_1186_s13053_022_00233_1 crossref_primary_10_1111_pin_70004 crossref_primary_10_1016_j_heliyon_2024_e25568 crossref_primary_10_1093_ajcp_aqae094 crossref_primary_10_1016_j_ejogrb_2022_06_001 crossref_primary_10_3390_genes13111953 crossref_primary_10_3390_ijms23158726 crossref_primary_10_1158_1078_0432_CCR_21_2027 crossref_primary_10_1200_EDBK_390738 crossref_primary_10_1007_s10689_023_00345_0 crossref_primary_10_1016_j_jdcr_2024_06_023 crossref_primary_10_3389_fonc_2022_1004469 crossref_primary_10_1016_j_humpath_2022_12_016 crossref_primary_10_1158_1078_0432_CCR_19_1324 crossref_primary_10_1186_s13256_024_04522_2 crossref_primary_10_1016_j_humpath_2021_10_004 crossref_primary_10_1097_CCO_0000000000000617 crossref_primary_10_1111_cas_14500 crossref_primary_10_1002_mgg3_886 crossref_primary_10_1007_s12672_022_00538_6 crossref_primary_10_1016_j_gim_2022_02_016 crossref_primary_10_1158_2159_8290_CD_20_1508 crossref_primary_10_1186_s12885_023_11607_6 crossref_primary_10_3390_cancers15245788 crossref_primary_10_3390_jcm13216419 crossref_primary_10_1136_bmjgast_2019_000274 crossref_primary_10_1002_jgc4_1546 crossref_primary_10_1177_17588359221118019 crossref_primary_10_1038_s41467_022_35592_9 crossref_primary_10_2217_crc_2020_0020 crossref_primary_10_1038_s41374_021_00694_3 crossref_primary_10_1002_cncr_35473 crossref_primary_10_1002_pros_24343 crossref_primary_10_1016_j_ctrv_2025_102890 crossref_primary_10_1002_mgg3_2104 crossref_primary_10_1016_j_bulcan_2022_06_010 crossref_primary_10_1016_j_ctrv_2020_102024 crossref_primary_10_3389_fphar_2023_1113182 crossref_primary_10_1053_j_gastro_2019_09_045 crossref_primary_10_1007_s12094_019_02272_y crossref_primary_10_1016_j_ctrv_2024_102821 crossref_primary_10_14309_ajg_0000000000003369 crossref_primary_10_1002_humu_24462 crossref_primary_10_3390_cells12071049 crossref_primary_10_1002_gcc_23015 crossref_primary_10_1111_jcmm_16149 crossref_primary_10_3390_jmp2020009 crossref_primary_10_1002_jcla_25085 crossref_primary_10_3390_cancers14153674 crossref_primary_10_5306_wjco_v14_i2_40 crossref_primary_10_7759_cureus_67332 crossref_primary_10_1016_j_clcc_2019_05_007 crossref_primary_10_3390_cancers15205065 crossref_primary_10_1016_j_clcc_2022_01_003 crossref_primary_10_1007_s10147_019_01498_8 crossref_primary_10_3390_cancers16233970 crossref_primary_10_1007_s10147_022_02187_9 crossref_primary_10_1016_j_dld_2023_04_020 crossref_primary_10_1007_s12022_020_09622_5 crossref_primary_10_1038_s41598_025_03618_z crossref_primary_10_1038_s41588_024_01703_z crossref_primary_10_1038_s43018_020_0100_0 crossref_primary_10_3390_biomedicines9040414 crossref_primary_10_3389_fonc_2022_827822 crossref_primary_10_3390_diagnostics14111076 crossref_primary_10_1038_s41379_019_0414_6 crossref_primary_10_1177_10668969241311500 crossref_primary_10_1002_gcc_23023 crossref_primary_10_1016_j_ygyno_2020_10_003 crossref_primary_10_1038_s41431_022_01134_6 crossref_primary_10_1007_s00595_022_02558_9 crossref_primary_10_1053_j_gastro_2025_06_001 crossref_primary_10_1002_tre_883 crossref_primary_10_3390_cancers13030406 crossref_primary_10_3389_fonc_2023_1277233 crossref_primary_10_3390_ijms241411437 crossref_primary_10_1016_j_giec_2021_09_002 crossref_primary_10_3389_fonc_2025_1560450 crossref_primary_10_3390_ijms26157138 crossref_primary_10_1016_j_trsl_2023_05_004 crossref_primary_10_1038_s41379_021_00918_3 crossref_primary_10_1007_s00292_019_0610_7 crossref_primary_10_1007_s11547_023_01590_0 crossref_primary_10_1007_s10147_024_02609_w crossref_primary_10_1007_s10147_021_01922_y crossref_primary_10_1038_s41416_020_01114_x crossref_primary_10_3390_cancers16010056 crossref_primary_10_4251_wjgo_v14_i3_654 crossref_primary_10_1007_s00292_021_00944_7 crossref_primary_10_1038_s41571_025_01054_6 crossref_primary_10_1146_annurev_cancerbio_061421_012927 crossref_primary_10_3390_ijms23031205 crossref_primary_10_3390_cancers14194804 crossref_primary_10_1007_s00761_020_00884_6 crossref_primary_10_1007_s00428_019_02701_x crossref_primary_10_1158_1078_0432_CCR_22_3956 crossref_primary_10_3892_ol_2023_14142 crossref_primary_10_1002_cam4_4525 crossref_primary_10_1111_cas_14798 crossref_primary_10_3390_cancers15092552 crossref_primary_10_3389_pore_2024_1611719 crossref_primary_10_1016_j_bpg_2022_101800 crossref_primary_10_1038_s41416_022_01754_1 crossref_primary_10_1080_21645515_2025_2471226 crossref_primary_10_1186_s12935_019_1091_8 crossref_primary_10_1186_s13053_020_00155_w crossref_primary_10_1186_s13053_021_00192_z crossref_primary_10_1007_s00432_022_04261_1 crossref_primary_10_1159_000547331 crossref_primary_10_1097_MOU_0000000000001242 crossref_primary_10_1007_s11523_024_01088_3 crossref_primary_10_1016_j_ejmg_2022_104479 crossref_primary_10_3390_cancers12123792 crossref_primary_10_3389_fonc_2025_1552411 crossref_primary_10_1016_j_cllc_2023_05_007 crossref_primary_10_1245_s10434_024_16621_x crossref_primary_10_1007_s12094_021_02752_0 crossref_primary_10_3390_ijms232113129 crossref_primary_10_1007_s13402_023_00912_8 crossref_primary_10_3389_fimmu_2025_1611890 crossref_primary_10_1002_cac2_12516 crossref_primary_10_1002_cam4_3688 crossref_primary_10_3390_cancers17040682 crossref_primary_10_3892_ol_2023_14155 crossref_primary_10_1038_s41525_023_00374_9 crossref_primary_10_1007_s12020_022_03031_w crossref_primary_10_1308_rcsann_2024_0024 crossref_primary_10_1016_j_gendis_2025_101717 crossref_primary_10_1016_j_cllc_2025_03_012 crossref_primary_10_1093_jnci_djad074 crossref_primary_10_1186_s40425_019_0722_x crossref_primary_10_1007_s13691_023_00622_w crossref_primary_10_1016_j_cancergen_2022_02_010 crossref_primary_10_3389_fonc_2023_1178772 crossref_primary_10_1038_s41698_024_00560_7 crossref_primary_10_3389_pore_2022_1610206 crossref_primary_10_1186_s41747_024_00484_8 crossref_primary_10_1038_s41588_021_00949_1 crossref_primary_10_1016_j_annonc_2020_03_299 crossref_primary_10_7759_cureus_37239 crossref_primary_10_1016_j_ejca_2024_114256 crossref_primary_10_1016_j_ebiom_2020_103060 crossref_primary_10_1016_j_soc_2021_06_008 crossref_primary_10_1002_jgc4_1392 crossref_primary_10_1016_j_dnarep_2025_103822 crossref_primary_10_3390_ijms21249504 crossref_primary_10_1136_jclinpath_2020_207040 crossref_primary_10_1136_jclinpath_2020_207281 crossref_primary_10_1016_j_critrevonc_2023_104055 crossref_primary_10_1080_2162402X_2024_2384667 crossref_primary_10_1093_oncolo_oyaf020 crossref_primary_10_4251_wjgo_v17_i6_107568 crossref_primary_10_3389_fonc_2023_1131011 crossref_primary_10_3389_fimmu_2022_1097730 crossref_primary_10_1007_s00129_021_04774_9 crossref_primary_10_1111_ijd_17602 crossref_primary_10_3389_fonc_2020_00666 crossref_primary_10_3390_cancers15082288 crossref_primary_10_3389_fonc_2023_1115241 crossref_primary_10_3389_fonc_2023_1126476 crossref_primary_10_1590_1678_4324_2025240708 crossref_primary_10_1007_s12149_023_01869_2 crossref_primary_10_1016_j_yamp_2020_07_019 crossref_primary_10_3390_cancers15184564 crossref_primary_10_1038_s10038_025_01345_x crossref_primary_10_1093_jjco_hyaa207 crossref_primary_10_1053_j_gastro_2021_09_071 crossref_primary_10_14309_ctg_0000000000000397 crossref_primary_10_1039_D5TB01409C crossref_primary_10_1111_bju_15566 crossref_primary_10_1080_15384101_2019_1638192 crossref_primary_10_3892_ol_2023_14012 crossref_primary_10_1177_11782234211039433 crossref_primary_10_3390_cancers15020506 crossref_primary_10_2196_48380 crossref_primary_10_3389_fonc_2024_1339302 crossref_primary_10_3389_fonc_2023_1127683 crossref_primary_10_1038_s41598_022_21500_0 crossref_primary_10_1177_17562848211024460 crossref_primary_10_3389_fonc_2022_774202 crossref_primary_10_1002_jso_26359 crossref_primary_10_1016_j_giec_2021_08_002 crossref_primary_10_1016_j_acra_2025_07_050 crossref_primary_10_1200_PO_24_00908 crossref_primary_10_1038_s41416_022_01972_7 crossref_primary_10_3389_fonc_2022_795129 crossref_primary_10_1097_MPA_0000000000001742 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1200/JCO.18.00283 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | 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: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1527-7755 |
| ExternalDocumentID | 30376427 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GeographicLocations | New York City |
| GeographicLocations_xml | – name: New York City |
| GrantInformation_xml | – fundername: NCI NIH HHS grantid: P30 CA008748 – fundername: NCI NIH HHS grantid: P50 CA092629 |
| GroupedDBID | --- .55 0R~ 18M 2WC 34G 39C 4.4 53G 5GY 5RE 8F7 AAQQT AARDX AAWTL AAYEP AAYOK ABJNI ABOCM ACGFO ACGFS ACGUR ADBBV AEGXH AENEX AIAGR ALMA_UNASSIGNED_HOLDINGS AWKKM BAWUL BYPQX C45 CGR CS3 CUY CVF DIK EBS ECM EIF EJD F5P F9R FBNNL FD8 GX1 H13 HZ~ IH2 K-O KQ8 L7B LSO MJL N9A NPM O9- OK1 OVD OWW P2P QTD R1G RHI RLZ RUC SJN SV3 TEORI TR2 TWZ UDS VVN WH7 X7M YCJ YFH YQY 7X8 ABBLC |
| ID | FETCH-LOGICAL-c384t-42b5200b04386f0cab72842f0ff9b28672e1d789fbec61d4a80bf3581713e7082 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 468 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000457744000005&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1527-7755 |
| IngestDate | Wed Oct 01 17:21:52 EDT 2025 Thu Jan 02 22:59:08 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 4 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c384t-42b5200b04386f0cab72842f0ff9b28672e1d789fbec61d4a80bf3581713e7082 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/6553803 |
| PMID | 30376427 |
| PQID | 2127659650 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2127659650 pubmed_primary_30376427 |
| PublicationCentury | 2000 |
| PublicationDate | 2019-02-01 |
| PublicationDateYYYYMMDD | 2019-02-01 |
| PublicationDate_xml | – month: 02 year: 2019 text: 2019-02-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Journal of clinical oncology |
| PublicationTitleAlternate | J Clin Oncol |
| PublicationYear | 2019 |
| References | 31586568 - Gastroenterology. 2019 Nov;157(5):1432-1434 30951645 - J Clin Oncol. 2019 Apr 10;37(11):942 30550362 - J Clin Oncol. 2019 Feb 1;37(4):263-265 32266124 - Transl Cancer Res. 2019 Dec;8(Suppl 6):S559-S563 |
| References_xml | – reference: 32266124 - Transl Cancer Res. 2019 Dec;8(Suppl 6):S559-S563 – reference: 31586568 - Gastroenterology. 2019 Nov;157(5):1432-1434 – reference: 30550362 - J Clin Oncol. 2019 Feb 1;37(4):263-265 – reference: 30951645 - J Clin Oncol. 2019 Apr 10;37(11):942 |
| SSID | ssj0014835 |
| Score | 2.6964076 |
| Snippet | Microsatellite instability (MSI) and/or mismatch repair deficiency (MMR-D) testing has traditionally been performed in patients with colorectal (CRC) and... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 286 |
| SubjectTerms | Biomarkers, Tumor - genetics Colorectal Neoplasms, Hereditary Nonpolyposis - epidemiology Colorectal Neoplasms, Hereditary Nonpolyposis - genetics Colorectal Neoplasms, Hereditary Nonpolyposis - pathology DNA Mismatch Repair Female Genetic Predisposition to Disease Humans Male Microsatellite Instability Middle Aged Mutation New York City - epidemiology Phenotype Prevalence Prospective Studies Transcriptome |
| Title | Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/30376427 https://www.proquest.com/docview/2127659650 |
| Volume | 37 |
| WOSCitedRecordID | wos000457744000005&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8NAEF7UinjxUV_1xQrSU2PTPHY3J5FiUbE1YKW9lWQftJekNlHIv3c22ZKTIHjJLRB2v-x8szPzfQjdCpepAJiDxQICCYprC23k7lqR4kDObaV5eGk2QUcjNp0Goblwy0xb5fpMLA9qkXJ9R97VSuTED4BQ3C8_Le0apaurxkJjEzVcoDIa1XRaVxE8VhpsaudWYJG-bxrfARjdl_7bXa9qo3R_J5dlkBns__fzDtCeoZf4ocLDIdqQSRPtDE0BvYnaYSVVXXTwuJ68yjq4jcNaxLo4QpOh7tTLolKwM5dYNxVUkt4Ffs7welelwJNFPsdAI3FYTjJxiVOFX4uEz_G7kUPAYZRYfY2v1TH6GDyO-0-WMWGwuMu83PKcWCszxbpiSJTNo5hCRHOUrVQQO4xQR_YEZYECMJCe8CJmx0qLqkH2KykQjBO0laSJPEM4FlKPaguPMNdjPmHcZw7kZw7zFVeMtNDNem1nAHJduYgSmX5ls3p1W-i02qDZslLjmEEMppBE0fM_vH2BdoHwBFXX9SVqKPjF5RXa5t_5Iltdl-iB5ygc_gAChcz5 |
| linkProvider | ProQuest |
| 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=Microsatellite+Instability+Is+Associated+With+the+Presence+of+Lynch+Syndrome+Pan-Cancer&rft.jtitle=Journal+of+clinical+oncology&rft.au=Latham%2C+Alicia&rft.au=Srinivasan%2C+Preethi&rft.au=Kemel%2C+Yelena&rft.au=Shia%2C+Jinru&rft.date=2019-02-01&rft.eissn=1527-7755&rft.volume=37&rft.issue=4&rft.spage=286&rft_id=info:doi/10.1200%2FJCO.18.00283&rft_id=info%3Apmid%2F30376427&rft_id=info%3Apmid%2F30376427&rft.externalDocID=30376427 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1527-7755&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1527-7755&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1527-7755&client=summon |