Molecular Background of Colorectal Tumors From Patients With Lynch Syndrome Associated With Germline Variants in PMS2
Uloženo v:
| Název: | Molecular Background of Colorectal Tumors From Patients With Lynch Syndrome Associated With Germline Variants in PMS2 |
|---|---|
| Autoři: | Broeke, S.W. ten, Bavel, T.C. van, Jansen, A.M.L., Gomez-Garcia, E., Hes, F.J., Hest, L.P. van, Letteboer, T.G.W., Olderode-Berends, M.J.W., Ruano, D., Spruijt, L., Suerink, M., Tops, C.M., Eijk, R. van, Morreau, H., Wezel, T. van, Nielsen, M. |
| Přispěvatelé: | Genetica Klinische Genetica, Child Health, Medical Genetics |
| Zdroj: | ten Broeke, S W, van Bavel, T C, Jansen, A M L, Gómez-García, E, Hes, F J, van Hest, L P, Letteboer, T G W, Olderode-Berends, M J W, Ruano, D, Spruijt, L, Suerink, M, Tops, C M, van Eijk, R, Morreau, H, van Wezel, T & Nielsen, M 2018, 'Molecular Background of Colorectal Tumors From Patients With Lynch Syndrome Associated With Germline Variants in PMS2', Gastroenterology, vol. 155, no. 3, pp. 844-851. https://doi.org/10.1053/j.gastro.2018.05.020 Gastroenterology, 155, 3, pp. 844-851 |
| Informace o vydavateli: | Elsevier BV, 2018. |
| Rok vydání: | 2018 |
| Témata: | Adult, Male, 0301 basic medicine, beta Catenin/genetics, MISMATCH-REPAIR DEFICIENCY, Radboud University Medical Center, Mismatch Repair, DNA Mismatch Repair, 03 medical and health sciences, Colorectal Neoplasms, Hereditary Nonpolyposis/genetics, Journal Article, Genetics, TUMORIGENESIS, Humans, Germ-Line Mutation, beta Catenin, Aged, Mismatch Repair Endonuclease PMS2, 0303 health sciences, MutL Protein Homolog 1/genetics, Hepatology, Colon Cancer, HUMAN CANCER, MUTATIONS, Epithelial Cell Adhesion Molecule/genetics, Research Support, Non-U.S. Gov't, CATENIN, Gastroenterology, Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences, Mismatch Repair Endonuclease PMS2/genetics, Middle Aged, Epithelial Cell Adhesion Molecule, 16. Peace & justice, Colorectal Neoplasms/genetics, Colorectal Neoplasms, Hereditary Nonpolyposis, 3. Good health, DNA-Binding Proteins, INTEGRATIVE GENOMICS VIEWER, CARCINOMAS, Human Genetics - Radboud University Medical Center, Female, Wnt Signaling, Colorectal Neoplasms, MutL Protein Homolog 1, DNA-Binding Proteins/genetics |
| Popis: | Germline variants in mismatch repair genes MLH1, MSH2 (EPCAM), MSH6, or PMS2 cause Lynch syndrome. Patients with these variants have an increased risk of developing colorectal cancers (CRCs) that differ from sporadic CRCs in genetic and histologic features. It has been a challenge to study CRCs associated with PMS2 variants (PMS2-associated CRCs) because these develop less frequently and in older patients than CRCs with variants in other mismatch repair genes.We analyzed 20 CRCs associated with germline variants in PMS2, 22 sporadic CRCs, 18 CRCs with germline variants in MSH2, and 24 CRCs from patients with germline variants in MLH1. Tumor tissue blocks were collected from Dutch pathology departments in 2017. After extraction of tumor DNA, we used a platform designed to detect approximately 3,000 somatic hotspot variants in 55 genes (including KRAS, APC, CTNNB1, and TP53). Somatic variant frequencies were compared using the Fisher exact test.None of the PMS2-associated CRCs contained any somatic variants in the catenin-β1 gene (CTNNB1), which encodes β-catenin, whereas 14 of 24 MLH1-associated CRCs (58%) contained variants in CTNNB1. Half the PMS2-associated CRCs contained KRAS variants, but only 20% of these were in hotspots that encoded G12D or G13D. These hotspot variants occurred more frequently in CRCs associated with variants in MLH1 (37.5%; P = .44) and MSH2 (71.4%; P = .035) than in those associated with variants in PMS2.In a genetic analysis of 84 colorectal tumors, we found tumors from patients with PMS2-associated Lynch syndrome to be distinct from colorectal tumors associated with defects in other mismatch repair genes. This might account for differences in development and less frequent occurrence. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2018.05.020 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/29758216 https://cris.maastrichtuniversity.nl/en/publications/7094cadc-dfea-4bf1-838a-d9197500b568 https://doi.org/10.1053/j.gastro.2018.05.020 https://cris.maastrichtuniversity.nl/en/publications/molecular-background-of-colorectal-tumors-from-patients-with-lync http://dspace.library.uu.nl/handle/1874/372144 https://www.ncbi.nlm.nih.gov/pubmed/29758216 https://research.vumc.nl/en/publications/molecular-background-of-colorectal-tumors-from-patients-with-lync https://research.rug.nl/en/publications/molecular-background-of-colorectal-tumors-from-patients-with-lync http://www.ncbi.nlm.nih.gov/pubmed/29758216 https://research.vumc.nl/en/publications/63370919-e9ca-4630-adbc-c8505f6410d7 https://dspace.library.uu.nl/handle/1874/372144 https://hdl.handle.net/1887/95564 https://hdl.handle.net/2066/195461 https://biblio.vub.ac.be/vubir/molecular-background-of-colorectal-tumors-from-patients-with-lynch-syndrome-associated-with-germline-variants-in-pms2(e3433ebb-bc6a-4687-b969-b1cc0aaec6c1).html |
| Rights: | Elsevier TDM |
| Přístupové číslo: | edsair.doi.dedup.....552620c3b6ba370c67ab3cb4a1b450d4 |
| Databáze: | OpenAIRE |
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstrakt: | Germline variants in mismatch repair genes MLH1, MSH2 (EPCAM), MSH6, or PMS2 cause Lynch syndrome. Patients with these variants have an increased risk of developing colorectal cancers (CRCs) that differ from sporadic CRCs in genetic and histologic features. It has been a challenge to study CRCs associated with PMS2 variants (PMS2-associated CRCs) because these develop less frequently and in older patients than CRCs with variants in other mismatch repair genes.We analyzed 20 CRCs associated with germline variants in PMS2, 22 sporadic CRCs, 18 CRCs with germline variants in MSH2, and 24 CRCs from patients with germline variants in MLH1. Tumor tissue blocks were collected from Dutch pathology departments in 2017. After extraction of tumor DNA, we used a platform designed to detect approximately 3,000 somatic hotspot variants in 55 genes (including KRAS, APC, CTNNB1, and TP53). Somatic variant frequencies were compared using the Fisher exact test.None of the PMS2-associated CRCs contained any somatic variants in the catenin-β1 gene (CTNNB1), which encodes β-catenin, whereas 14 of 24 MLH1-associated CRCs (58%) contained variants in CTNNB1. Half the PMS2-associated CRCs contained KRAS variants, but only 20% of these were in hotspots that encoded G12D or G13D. These hotspot variants occurred more frequently in CRCs associated with variants in MLH1 (37.5%; P = .44) and MSH2 (71.4%; P = .035) than in those associated with variants in PMS2.In a genetic analysis of 84 colorectal tumors, we found tumors from patients with PMS2-associated Lynch syndrome to be distinct from colorectal tumors associated with defects in other mismatch repair genes. This might account for differences in development and less frequent occurrence. |
|---|---|
| ISSN: | 00165085 |
| DOI: | 10.1053/j.gastro.2018.05.020 |