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

Autor: Halabi NM; Department of Genetic Medicine, Weill-Cornell Medical College, New York, United States of America., Martinez A; Surgery Department, Institute Claudius Regaud, Toulouse, France., Al-Farsi H; Department of Genetic Medicine, Weill-Cornell Medical College, New York, United States of America., Mery E; Pathology Department, Institute Claudius Regaud, Toulouse, France., Puydenus L; Pathology Department, Institute Claudius Regaud, Toulouse, France., Pujol P; Oncogenetics, Centre Hospitalier Regional Universitaire de Montpellier, Montpellier, France., Khalak HG; Advanced Computing, Weill-Cornell Medical College in Qatar, Doha, Qatar., McLurcan C; Biosciences Department, University of Birmingham, Birmingham, United Kingdom., Ferron G; Surgery Department, Institute Claudius Regaud, Toulouse, France., Querleu D; Surgery Department, Institute Claudius Regaud, Toulouse, France., Al-Azwani I; Genomics Core, Weill-Cornell Medical in Qatar, Doha, Qatar., Al-Dous E; Genomics Core, Weill-Cornell Medical in Qatar, Doha, Qatar., Mohamoud YA; Genomics Core, Weill-Cornell Medical in Qatar, Doha, Qatar., Malek JA; Department of Genetic Medicine, Weill-Cornell Medical College, New York, United States of America.; Genomics Core, Weill-Cornell Medical in Qatar, Doha, Qatar., Rafii A; Department of Genetic Medicine, Weill-Cornell Medical College, New York, United States of America.; Stem Cells and Microenvironment Laboratory, Weill-Cornell Medical College in Qatar, Doha, Qatar.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2016 Jan 06; Vol. 12 (1), pp. e1005755. Date of Electronic Publication: 2016 Jan 06 (Print Publication: 2016).
DOI: 10.1371/journal.pgen.1005755
Abstrakt: 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.
Databáze: MEDLINE
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