Genomic and functional overlap between somatic and germline chromosomal rearrangements.

Autor:	van Heesch S; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Simonis M; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., van Roosmalen MJ; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Pillalamarri V; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA., Brand H; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA., Kuijk EW; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., de Luca KL; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Lansu N; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Braat AK; Department of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands., Menelaou A; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Hao W; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Korving J; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Snijder S; Department of Clinical Genetics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands., van der Veken LT; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Hochstenbach R; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Knegt AC; Department of Clinical Genetics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands., Duran K; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Renkens I; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Alekozai N; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Jager M; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Vergult S; Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium., Menten B; Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium., de Bruijn E; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Boymans S; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands., Ippel E; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., van Binsbergen E; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Talkowski ME; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA., Lichtenbelt K; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands., Cuppen E; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands. Electronic address: e.cuppen@hubrecht.eu., Kloosterman WP; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands. Electronic address: w.kloosterman@umcutrecht.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2014 Dec 24; Vol. 9 (6), pp. 2001-10. Date of Electronic Publication: 2014 Dec 11.
DOI:	10.1016/j.celrep.2014.11.022
Abstrakt:	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. (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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