title: Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer.
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.
authors.affiliation: Department of Genetic Medicine, Weill-Cornell Medical College, New York, United States of America.
authors.forename: Najeeb M
authors.initials: NM
authors.lastname: Halabi
authors.affiliation: Surgery Department, Institute Claudius Regaud, Toulouse, France.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martinez
authors.affiliation: Department of Genetic Medicine, Weill-Cornell Medical College, New York, United States of America.
authors.forename: Halema
authors.initials: H
authors.lastname: Al-Farsi
authors.affiliation: Pathology Department, Institute Claudius Regaud, Toulouse, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Mery
authors.affiliation: Pathology Department, Institute Claudius Regaud, Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Puydenus
authors.affiliation: Oncogenetics, Centre Hospitalier Regional Universitaire de Montpellier, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.affiliation: Advanced Computing, Weill-Cornell Medical College in Qatar, Doha, Qatar.
authors.forename: Hanif G
authors.initials: HG
authors.lastname: Khalak
authors.affiliation: Biosciences Department, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Cameron
authors.initials: C
authors.lastname: McLurcan
authors.affiliation: Surgery Department, Institute Claudius Regaud, Toulouse, France.
authors.forename: Gwenael
authors.initials: G
authors.lastname: Ferron
authors.affiliation: Surgery Department, Institute Claudius Regaud, Toulouse, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Querleu
authors.affiliation: Genomics Core, Weill-Cornell Medical in Qatar, Doha, Qatar.
authors.forename: Iman
authors.initials: I
authors.lastname: Al-Azwani
authors.affiliation: Genomics Core, Weill-Cornell Medical in Qatar, Doha, Qatar.
authors.forename: Eman
authors.initials: E
authors.lastname: Al-Dous
authors.affiliation: Genomics Core, Weill-Cornell Medical in Qatar, Doha, Qatar.
authors.forename: Yasmin A
authors.initials: YA
authors.lastname: Mohamoud
authors.affiliation: Department of Genetic Medicine, Weill-Cornell Medical College, New York, United States of America.|Genomics Core, Weill-Cornell Medical in Qatar, Doha, Qatar.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Malek
authors.affiliation: 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.
authors.forename: Arash
authors.initials: A
authors.lastname: Rafii
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005854:Germ Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome
chemical_list: D009363:Neoplasm Proteins