Exome sequencing of familial adenomatous polyposis‐like individuals identifies both known and novel causative genes. Issue 4 (26th July 2021)

• Record Type: Journal Article
• Authors: Xavier, Alexandre; Scott, Rodney J.; Talseth‐Palmer, Bente
• Is Part Of: Clinical genetics. Volume 100:Issue 4(2021)
• Page Start: 478
• Page End: 483
• Publication Date: 2021-07-26
• Subjects: colorectal cancer -- familial cancer -- inherited cancer -- polyposis -- sequencing; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.14029
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: 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. Abstract :