Constitutional chromothripsis of the <i>APC</i> locus as a cause of genetic predisposition to colon cancer

Abstract

Based on comprehensive genomic analysis, we propose that constitutional chromothripsis dampening <i>APC</i> expression, possibly modified by additional <i>APC</i>-Axin-GSK3B-β-catenin pathway disruptions, underlies the patient's clinical phenotype. The combinatorial approach we deployed provides a powerful tool set for deciphering unsolved familial polyposis and potentially other tumour syndromes and monogenic diseases.