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PLoS Genet. 2016 Jan 6;12(1):e1005755. doi: 10.1371/journal.pgen.1005755. eCollection 2016 Jan.

Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer.

Author information

1
Department of Genetic Medicine, Weill-Cornell Medical College, New York, United States of America.
2
Surgery Department, Institute Claudius Regaud, Toulouse, France.
3
Pathology Department, Institute Claudius Regaud, Toulouse, France.
4
Oncogenetics, Centre Hospitalier Regional Universitaire de Montpellier, Montpellier, France.
5
Advanced Computing, Weill-Cornell Medical College in Qatar, Doha, Qatar.
6
Biosciences Department, University of Birmingham, Birmingham, United Kingdom.
7
Genomics Core, Weill-Cornell Medical in Qatar, Doha, Qatar.
8
Stem Cells and Microenvironment Laboratory, Weill-Cornell Medical College in Qatar, Doha, Qatar.

Abstract

Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients, and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those genes could lead to new therapeutic strategies.

PMID:
26735499
PMCID:
PMC4703369
DOI:
10.1371/journal.pgen.1005755
[Indexed for MEDLINE]
Free PMC Article

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