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Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing.

Authors :
Jiao X
Hooper SD
Djureinovic T
Larsson C
Wärnberg F
Tellgren-Roth C
Botling J
Sjöblom T
Source :
BMC genomics [BMC Genomics] 2013 Mar 12; Vol. 14, pp. 165. Date of Electronic Publication: 2013 Mar 12.
Publication Year :
2013

Abstract

Background: Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing.<br />Results: We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology.<br />Conclusions: Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells.

Details

Language :
English
ISSN :
1471-2164
Volume :
14
Database :
MEDLINE
Journal :
BMC genomics
Publication Type :
Academic Journal
Accession number :
23496902
Full Text :
https://doi.org/10.1186/1471-2164-14-165