ZFIN ID: ZDB-PUB-170214-248
Genomic and functional overlap between somatic and germline chromosomal rearrangements
van Heesch, S., Simonis, M., van Roosmalen, M.J., Pillalamarri, V., Brand, H., Kuijk, E.W., de Luca, K.L., Lansu, N., Braat, A.K., Menelaou, A., Hao, W., Korving, J., Snijder, S., van der Veken, L.T., Hochstenbach, R., Knegt, A.C., Duran, K., Renkens, I., Alekozai, N., Jager, M., Vergult, S., Menten, B., de Bruijn, E., Boymans, S., Ippel, E., van Binsbergen, E., Talkowski, M.E., Lichtenbelt, K., Cuppen, E., Kloosterman, W.P.
Date: 2014
Source: Cell Reports   9: 2001-10 (Journal)
Registered Authors: Braat, Koen, Cuppen, Edwin, de Bruijn, Ewart, Kloosterman, Wigard
Keywords: none
MeSH Terms:
  • Animals
  • Chromosome Aberrations*
  • Chromosome Breakpoints
  • Chromosomes, Human/genetics*
  • Congenital Abnormalities/genetics*
  • DNA-Binding Proteins/genetics
  • Forkhead Transcription Factors/genetics
  • Gene Rearrangement*
  • Genome, Human*
  • Germ-Line Mutation*
  • HEK293 Cells
  • Humans
  • MicroRNAs/genetics
  • Repressor Proteins/genetics
  • Transcription Factors/genetics
  • Zebrafish
PubMed: 25497101 Full text @ Cell Rep.
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.