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

Najeeb Halabi, Alejandra Martinez, Halema Al-Farsi, Eliane Mery, Laurence Puydenus, Pascal Pujol, Hanif G. Khalak, Cameron McLurcan, Gwenael Ferron, Denis Querleu, Iman Al Azwani, Eman Aldous, Yasmin Ali Mohamoud, Joel Malek, Arash Rafii Tabrizi

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article numbere1005755
JournalPLoS Genetics
Volume12
Issue number1
DOIs
Publication statusPublished - 2016

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ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

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