Genomic and Functional Overlap between Somatic and Germline Chromosomal Rearrangements
0301 basic medicine
QH301-705.5
AUTISM SPECTRUM DISORDERS
DE-NOVO
Congenital Abnormalities
Chromosome Breakpoints
03 medical and health sciences
Animals
Chromosomes, Human
Humans
Biology (General)
Germ-Line Mutation
Zebrafish
COPY NUMBER VARIATION
REPAIR
Chromosome Aberrations
Gene Rearrangement
ETV1
IDENTIFICATION
ABNORMALITIES
Genome, Human
Biology and Life Sciences
Forkhead Transcription Factors
GENE FUSIONS
Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences
PROSTATE-CANCER
3. Good health
STRUCTURAL VARIATION
DNA-Binding Proteins
Repressor Proteins
MicroRNAs
HEK293 Cells
Transcription Factors
DOI:
10.1016/j.celrep.2014.11.022
Publication Date:
2014-12-11T13:41:13Z
AUTHORS (30)
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.
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CITATIONS (19)
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