Premium
Use of multigene‐panel identifies pathogenic variants in several CRC ‐predisposing genes in patients previously tested for Lynch Syndrome
Author(s) -
Hansen Maren F.,
Johansen Jostein,
Sylvander Anna E.,
Bjørnevoll Inga,
TalsethPalmer Bente A.,
Lavik Liss A. S.,
Xavier Alexandre,
Engebretsen Lars F.,
Scott Rodney J.,
Drabløs Finn,
Sjursen Wenche
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12994
Subject(s) - lynch syndrome , sanger sequencing , genetics , gene , germline , colorectal cancer , candidate gene , germline mutation , biology , cancer , mutation , dna mismatch repair
Background Many families with a high burden of colorectal cancer fulfil the clinical criteria for Lynch Syndrome. However, in about half of these families, no germline mutation in the mismatch repair genes known to be associated with this disease can be identified. The aim of this study was to find the genetic cause for the increased colorectal cancer risk in these unsolved cases. Materials and methods To reach the aim, we designed a gene panel targeting 112 previously known or candidate colorectal cancer susceptibility genes to screen 274 patient samples for mutations. Mutations were validated by Sanger sequencing and, where possible, segregation analysis was performed. Results We identified 73 interesting variants, of whom 17 were pathogenic and 19 were variants of unknown clinical significance in well‐established cancer susceptibility genes. In addition, 37 potentially pathogenic variants in candidate colorectal cancer susceptibility genes were detected. Conclusion In conclusion, we found a promising DNA variant in more than 25 % of the patients, which shows that gene panel testing is a more effective method to identify germline variants in CRC patients compared to a single gene approach.