title: Integrative analysis of copy number alteration and gene expression profiling in ovarian clear cell adenocarcinoma.
abstract: Ovarian clear cell adenocarcinoma (Ov-CCA) is a distinctive subtype of ovarian epithelial carcinoma. In this study, we performed array comparative genomic hybridization (aCGH) and paired gene expression microarray of 19 fresh-frozen samples and conducted integrative analysis. For the copy number alterations, significantly amplified regions (false discovery rate [FDR] q <0.05) were 1q21.3 and 8q24.3, and significantly deleted regions were 3p21.31, 4q12, 5q13.2, 5q23.2, 5q31.1, 7p22.1, 7q11.23, 8p12, 9p22.1, 11p15.1, 12p13.31, 15q11.2, 15q21.2, 18p11.31, and 22q11.21 using the Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. Integrative analysis revealed 94 genes demonstrating frequent copy number alterations (>25% of samples) that correlated with gene expression (FDR <0.05). These genes were mainly located on 8p11.21, 8p21.2-p21.3, 8q22.1, 8q24.3, 17q23.2-q23.3, 19p13.3, and 19p13.11. Among the regions, 8q24.3 was found to contain the most genes (30 of 94 genes) including PTK2. The 8q24.3 region was indicated as the most significant region, as supported by copy number, GISTIC, and integrative analysis. Pathway analysis using differentially expressed genes on 8q24.3 revealed several major nodes, including PTK2. In conclusion, we identified a set of 94 candidate genes with frequent copy number alterations that correlated with gene expression. Specific chromosomal alterations, such as the 8q24.3 gain containing PTK2, could be a therapeutic target in a subset of Ov-CCAs.
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Chang Ohk
authors.initials: CO
authors.lastname: Sung
authors.forename: Chel Hun
authors.initials: CH
authors.lastname: Choi
authors.forename: Young-Hyeh
authors.initials: YH
authors.lastname: Ko
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Ju
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.forename: Nyunsu
authors.initials: N
authors.lastname: Kim
authors.forename: So Young
authors.initials: SY
authors.lastname: Kang
authors.forename: Sang Yun
authors.initials: SY
authors.lastname: Ha
authors.forename: Kyusam
authors.initials: K
authors.lastname: Choi
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Bae
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Tae-Joong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Song
authors.forename: Byoung-Gie
authors.initials: BG
authors.lastname: Kim
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: PTK2; aCGH; clear cell carcinoma; expression microarray; ovary