Intraindividual genomic heterogeneity of high‐grade serous carcinoma of the ovary and clinical utility of ascitic cancer cells for mutation profiling

• DOI: 10.1002/path.4819
• Publication Date: 2016-10-14T16:05:19Z
• Authors: Youn Jin Choi; Je‐Keun Rhee; Soo Young Hur; Min Sung Kim; Sung Hak Lee; Yeun‐Jun Chung; Tae‐Min Kim; Sug Hyung Lee
• Keywords: Serous carcinoma

Abstract Intraindividual tumoural heterogeneity (ITH) is a hallmark of solid tumours and impedes accurate genomic diagnosis selection proper therapy. The aim this study was to identify ITH ovarian high‐grade serous carcinomas (OSCs) determine the utility ascitic cancer cells as resource for mutation profiling in spite ITH. We performed whole‐exome sequencing, copy number DNA methylation four OSC genomes by using multiregional biopsies from 13 intraovarian lesions, 12 extraovarian tumour lesions (omentum/peritoneum), cells. observed substantial levels mutations alterations (CNAs) OSCs. categorized into ‘common’, ‘shared’ ‘private’ according regional distribution. Six common, eight shared 24 private were known cancer‐related genes. Common had higher mutant allele frequency, included TP53 all Region‐specific chromosomal amplifications deletions involving BRCA1 , PIK3CA RB1 also identified. It note that detected represented 92.3–100% overall somatic given case. Phylogenetic analyses predicted polyseeding origin Our results demonstrate that, despite ITH, mutations, CNAs methylations both ‘common’ category genes highly conserved OSCs, highlighting clinical relevance genome analysis Ascitic may serve potential discovering primary with diagnostic therapeutic relevance. Copyright © 2016 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.