Correction: Integrated Copy Number and Expression Analysis Identifies Profiles of Whole-Arm Chromosomal Alterations and Subgroups with Favorable Outcome in Ovarian Clear Cell Carcinomas

Ovarian clear cell carcinoma (CCC) is generally associated with chemoresistance and poor clinical outcome, even with early diagnosis; whereas high-grade serous carcinomas (SCs) and endometrioid carcinomas (ECs) are commonly chemosensitive at advanced stages. Although an integrated genomic analysis of SC has been performed, conclusive views on copy number and expression profiles for CCC are still limited. In this study, we performed single nucleotide polymorphism analysis with 57 epithelial ovarian cancers (31 CCCs, 14 SCs, and 12 ECs) and microarray expression analysis with 55 cancers (25 CCCs, 16 SCs, and 14 ECs). We then evaluated PIK3CAmutations and ARID1A expression in CCCs. SNP array analysis classified 13% of CCCs into a cluster with high frequency and focal range of copy number alterations (CNAs), significantly lower than for SCs (93%, P < 0.01) and ECs (50%, P = 0.017). The ratio of whole-arm to all CNAs was higher in CCCs (46.9%) than SCs (21.7%; P < 0.0001). SCs with loss of heterozygosity (LOH) of BRCA1 (85%) also had LOH of NF1 and TP53, and LOH of BRCA2 (62%) coexisted with LOH of RB1 and TP53. Microarray analysis classified CCCs into three clusters. One cluster (CCC-2, n = 10) showed more favorable prognosis than the CCC-1 and CCC-3 clusters (P = 0.041). Coexistent alterations of PIK3CA and ARID1A were more common in CCC-1 and CCC-3 (7/11, 64%) than in CCC2 (0/10, 0%; P < 0.01). Being in cluster CCC-2 was an independent favorable prognostic factor in CCC. In conclusion, CCC was characterized by a high ratio of whole-arm CNAs; whereas CNAs in SC were mainly focal, but preferentially caused LOH of well-known tumor PLOS ONE | DOI:10.1371/journal.pone. 0128066 June 4, 2015 1 / 18 OPEN ACCESS Citation: Uehara Y, Oda K, Ikeda Y, Koso T, Tsuji S, Yamamoto S, et al. (2015) Integrated Copy Number and Expression Analysis Identifies Profiles of WholeArm Chromosomal Alterations and Subgroups with Favorable Outcome in Ovarian Clear Cell Carcinomas. PLoS ONE 10(6): e0128066. doi:10.1371/journal.pone. 0128066 Academic Editor: Rolf Müller, Philipps University, GERMANY Received: September 3, 2014 Accepted: April 23, 2015 Published: June 4, 2015 Copyright: © 2015 Uehara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: The expression array data are freely available in the GEO website soon (The accession number is GSE65986 in GEO website (http://www.ncbi.nlm.nih.gov/geo/query/acc. cgi? acc=GSE65986). The SNP array data with detailed clinical information will be available upon request. The reason of the controlled access is because it includes genotpying information of each patient. The names of the individuals that readers may contact to request the data is Yuriko Uehara suppressor genes. As such, expression profiles might be useful for sub-classification of CCC, and might provide useful information on prognosis.