- Title
- Exome sequencing of familial adenomatous polyposis-like individuals identifies both known and novel causative genes
- Creator
- Xavier, Alexandre; Scott, Rodney J.; Talseth-Palmer, Bente
- Relation
- Clinical Genetics Vol. 100, Issue 4, p. 478-483
- Publisher Link
- http://dx.doi.org/10.1111/cge.14029
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2021
- Description
- Inherited polyposis syndromes are predominantly caused by pathogenic variants in APC and are linked to familial adenomatous polyposis (FAP). However, after clinical screening, 20%–30% of individuals diagnosed with FAP do not carry a pathogenic variant in APC (often categorised as FAP-like). Other known inherited adenomatous polyposis syndromes such as MUTYH, POLD1/E, or NTHL1-associated polyposis only account for, 3 a fraction of the remaining cases. A cohort of 48 individuals clinically diagnosed with a FAP-like phenotype was selected based on a strong family history of colorectal cancer and no previous pathogenic variant found in APC and/or MUTYH, by genetic screening. Using whole exome sequencing, FAP-like patients were found to carry pathogenic variants in MUTYH, APC, POLE and TP53, as well as DNA-repair genes and inflammation related genes. Additionally, a comprehensive assessment of copy number variation revealed two loci of interest that appeared to be associated with polyposis risk. In total, 6 out of 48 polyposis were explained through re-sequencing. This study highlights the potential role of DNA-repair as well as inflammation-related variants towards polyp development.
- Subject
- colorectal cancer; familial cancer; inherited cancer; polyposis; sequencing; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1472470
- Identifier
- uon:48845
- Identifier
- ISSN:0009-9163
- Language
- eng
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