title: Implication of genomic characterization in synchronous endometrial and ovarian cancers of endometrioid histology.
abstract: Synchronous endometrial and ovarian carcinomas (SEOCs) present gynecologic oncologists with a challenging diagnostic puzzle: discriminating between double primary cancers and single primary cancer with metastasis. We aimed to determine the clonal relationship between simultaneously diagnosed endometrial and ovarian carcinomas.
  
  
  
  Fourteen pairs of SEOCs of endometrioid type and two pairs of SEOCs with disparate histologic types (control for dual primary tumors) were subjected to massively parallel sequencing (MPS) and molecular inversion probe microarrays.
  
  
  
  Thirteen of the 14 pairs of SEOCs harbored somatic mutations shared by both uterine and ovarian lesions, indicative of clonality. High degree of chromosomal instability in the tumors from 10 patients who received adjuvant chemotherapy, of whom 9 had synchronous carcinomas with significantly overlapping copy number alterations (CNAs), suggestive of single primary tumors with metastasis. The clonal relationship determined by genomic analyses did not agree with clinicopathological criteria in 11 of 14 cases. Minimal CNAs were identified in both ovarian and endometrial carcinomas in 4 patients, who did not receive adjuvant chemotherapy and experienced no recurrent diseases. In contrast, two of the 10 patients with chromosomally unstable cancers developed recurrent tumors.
  
  
  
  Our findings support a recent paradigm-shifting concept that most SEOCs originate from a single tumor. It also casts doubt on the clinicopathological criteria used to distinguish between dual primary tumors and single primary tumor with metastasis. Testing of CNAs on SEOCs may help determining the need of adjuvant therapy.
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Angel
authors: A
authors: Chao
authors: Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Ren-Chin
authors: RC
authors: Wu
authors: Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Shih-Ming
authors: SM
authors: Jung
authors: Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taiwan; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan.
authors: Yun-Shien
authors: YS
authors: Lee
authors: ACTGenomics, Co. Ltd., Taiwan.
authors: Shu-Jen
authors: SJ
authors: Chen
authors: ACTGenomics, Co. Ltd., Taiwan.
authors: Yen-Lung
authors: YL
authors: Lu
authors: Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taiwan.
authors: Chia-Lung
authors: CL
authors: Tsai
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Chiao-Yun
authors: CY
authors: Lin
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Yun-Hsin
authors: YH
authors: Tang
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Ming-Yu
authors: MY
authors: Chen
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Huei-Jean
authors: HJ
authors: Huang
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Hung-Hsueh
authors: HH
authors: Chou
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Kuan-Gen
authors: KG
authors: Huang
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Ting-Chang
authors: TC
authors: Chang
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taiwan. Electronic address: knoxtn@cgmh.org.tw.
authors: Tzu-Hao
authors: TH
authors: Wang
authors: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. Electronic address: sh46erry@ms.hinet.com.
authors: Chyong-Huey
authors: CH
authors: Lai
mesh_terms: D000328:Adult; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology
keywords: Copy number alteration; Endometrial cancer; Massively parallel sequencing (MPS); Ovarian cancer; Synchronous