title: Detection of somatic copy number alterations in cancer using targeted exome capture sequencing.
abstract: The research community at large is expending considerable resources to sequence the coding region of the genomes of tumors and other human diseases using targeted exome capture (i.e., "whole exome sequencing"). The primary goal of targeted exome sequencing is to identify nonsynonymous mutations that potentially have functional consequences. Here, we demonstrate that whole-exome sequencing data can also be analyzed for comprehensively monitoring somatic copy number alterations (CNAs) by benchmarking the technique against conventional array CGH. A series of 17 matched tumor and normal tissues from patients with metastatic castrate-resistant prostate cancer was used for this assessment. We show that targeted exome sequencing reliably identifies CNAs that are common in advanced prostate cancer, such as androgen receptor (AR) gain and PTEN loss. Taken together, these data suggest that targeted exome sequencing data can be effectively leveraged for the detection of somatic CNAs in cancer.
authors: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
authors: Robert J
authors: RJ
authors: Lonigro
authors: Catherine S
authors: CS
authors: Grasso
authors: Dan R
authors: DR
authors: Robinson
authors: Xiaojun
authors: X
authors: Jing
authors: Yi-Mi
authors: YM
authors: Wu
authors: Xuhong
authors: X
authors: Cao
authors: Michael J
authors: MJ
authors: Quist
authors: Scott A
authors: SA
authors: Tomlins
authors: Kenneth J
authors: KJ
authors: Pienta
authors: Arul M
authors: AM
authors: Chinnaiyan
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D059472:Exome / Q000235:genetics; D018628:Gene Dosage; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human