Bibliographic Details
| Title: |
Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome |
| Authors: |
Nayê Balzan Schneider, Tatiane Pastor, André Escremim de Paula, Maria Isabel Achatz, Ândrea Ribeiro dos Santos, Fernanda Sales Luiz Vianna, Clévia Rosset, Manuela Pinheiro, Patricia Ashton‐Prolla, Miguel Ângelo Martins Moreira, Edenir Inêz Palmero, Brazilian Lynch Syndrome Study Group |
| Source: |
Cancer Medicine, Vol 7, Iss 5, Pp 2078-2088 (2018) |
| Publisher Information: |
Wiley, 2018. |
| Publication Year: |
2018 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Colorectal cancer, Lynch syndrome, MMR genes, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Abstract Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome, caused by germline mutations in one of the major genes involved in mismatch repair (MMR): MLH1, MSH2, MSH6 and more rarely, PMS2. Recently, germline deletions in EPCAM have been also associated to the syndrome. Most of the pathogenic MMR mutations found in LS families occur in MLH1 or MSH2. Gene variants include missense, nonsense, frameshift mutations, large genomic rearrangements and splice‐site variants and most of the studies reporting the molecular characterization of LS families have been conducted outside South America. In this study, we analyzed 60 unrelated probands diagnosed with colorectal cancer and LS criteria. Testing for germline mutations and/or rearrangements in the most commonly affected MMR genes (MLH1, MSH2, EPCAM and MSH6) was done by Sanger sequencing and MLPA. Pathogenic or likely pathogenic variants were identified in MLH1 or MSH2 in 21 probands (35.0%). Of these, approximately one‐third were gene rearrangements. In addition, nine variants of uncertain significance (VUS) were identified in 10 (16.6%) of the sixty probands analyzed. Other four novel variants were identified, only in MLH1. Our results suggest that MSH6 pathogenic variants are not common among Brazilian LS probands diagnosed with CRC and that MMR gene rearrangements account for a significant proportion of the germline variants in this population underscoring the need to include rearrangement analysis in the molecular testing of Brazilian individuals with suspected Lynch syndrome. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2045-7634 |
| Relation: |
https://doaj.org/toc/2045-7634 |
| DOI: |
10.1002/cam4.1316 |
| Access URL: |
https://doaj.org/article/cb5a310aee374f4c9feb6231d782cc58 |
| Accession Number: |
edsdoj.b5a310aee374f4c9feb6231d782cc58 |
| Database: |
Directory of Open Access Journals |
