| Literature DB >> 25497101 |
Sebastiaan van Heesch1, Marieke Simonis1, Markus J van Roosmalen2, Vamsee Pillalamarri3, Harrison Brand3, Ewart W Kuijk1, Kim L de Luca1, Nico Lansu1, A Koen Braat4, Androniki Menelaou2, Wensi Hao1, Jeroen Korving1, Simone Snijder5, Lars T van der Veken2, Ron Hochstenbach2, Alida C Knegt5, Karen Duran2, Ivo Renkens2, Najla Alekozai2, Myrthe Jager2, Sarah Vergult6, Björn Menten6, Ewart de Bruijn1, Sander Boymans1, Elly Ippel2, Ellen van Binsbergen2, Michael E Talkowski3, Klaske Lichtenbelt2, Edwin Cuppen7, Wigard P Kloosterman8.
Abstract
Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.Entities:
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Year: 2014 PMID： 25497101 DOI： 10.1016/j.celrep.2014.11.022
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423