- Title
- Detection of germline variants with pathogenic potential in 48 patients with familial colorectal cancer by using whole exome sequencing
- Creator
- Singh, Ashish Kumar; Talseth-Palmer, Bente; Xavier, Alexandre; Scott, Rodney J.; Drabløs, Finn; Sjursen, Wenche
- Relation
- BMC Medical Genomics Vol. 16, no. 126
- Publisher Link
- http://dx.doi.org/10.1186/s12920-023-01562-3
- Publisher
- BioMed Central (BMC)
- Resource Type
- journal article
- Date
- 2023
- Description
- Background: Hereditary genetic mutations causing predisposition to colorectal cancer are accountable for approximately 30% of all colorectal cancer cases. However, only a small fraction of these are high penetrant mutations occurring in DNA mismatch repair genes, causing one of several types of familial colorectal cancer (CRC) syndromes. Most of the mutations are low-penetrant variants, contributing to an increased risk of familial colorectal cancer, and they are often found in additional genes and pathways not previously associated with CRC. The aim of this study was to identify such variants, both high-penetrant and low-penetrant ones. Methods: We performed whole exome sequencing on constitutional DNA extracted from blood of 48 patients suspected of familial colorectal cancer and used multiple in silico prediction tools and available literature-based evidence to detect and investigate genetic variants. Results: We identified several causative and some potentially causative germline variants in genes known for their association with colorectal cancer. In addition, we identified several variants in genes not typically included in relevant gene panels for colorectal cancer, including CFTR, PABPC1 and TYRO3, which may be associated with an increased risk for cancer. Conclusions: Identification of variants in additional genes that potentially can be associated with familial colorectal cancer indicates a larger genetic spectrum of this disease, not limited only to mismatch repair genes. Usage of multiple in silico tools based on different methods and combined through a consensus approach increases the sensitivity of predictions and narrows down a large list of variants to the ones that are most likely to be significant.
- Subject
- whole exome sequencing (WES); colorectal cancer (CRC); Lynch syndrome (LS); familial colorectal cancer type X (FCCTX); mismatch repair (MMR); copy number variation (CNV); SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1488001
- Identifier
- uon:52322
- Identifier
- ISSN:1755-8794
- Rights
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Language
- eng
- Full Text
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