Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis

Familial Cancer
Isabel SpierStefan Aretz

Abstract

In up to 30% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, and POLE or POLD1, causing Polymerase-Proofreading-associated polyposis can be identified, although a hereditary etiology is likely. To uncover new causative genes, exome sequencing was performed using DNA from leukocytes and a total of 12 colorectal adenomas from seven unrelated patients with unexplained sporadic adenomatous polyposis. For data analysis and variant filtering, an established bioinformatics pipeline including in-house tools was applied. Variants were filtered for rare truncating point mutations and copy-number variants assuming a dominant, recessive, or tumor suppressor model of inheritance. Subsequently, targeted sequence analysis of the most promising candidate genes was performed in a validation cohort of 191 unrelated patients. All relevant variants were validated by Sanger sequencing. The analysis of exome sequencing data resulted in the identification of rare loss-of-function germline mutations in three promising candidate genes (DSC2, PIEZO1, ZSWIM7). In the validation cohort, further variants predicted to be pathoge...Continue Reading

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Citations

Sep 4, 2016·FEMS Yeast Research·Julieta Martino, Kara A Bernstein
Oct 17, 2016·Trends in Biochemical Sciences·Jason WuJörg Grandl
Oct 8, 2016·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Laura Valle
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May 19, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jia-Lin Yu, Hai-Yang Liao
Jun 29, 2021·The International Journal of Biochemistry & Cell Biology·Kuen Kuen LamPeh Yean Cheah

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