PMID- 26832770 OWN - NLM STAT- MEDLINE DCOM- 20160712 LR - 20190221 IS - 1460-2105 (Electronic) IS - 0027-8874 (Print) IS - 0027-8874 (Linking) VI - 108 IP - 6 DP - 2016 Jun TI - Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas. PG - djv427 LID - djv427 [pii] LID - 10.1093/jnci/djv427 [doi] AB - Synchronous early-stage endometrioid endometrial carcinomas (EECs) and endometrioid ovarian carcinomas (EOCs) are associated with a favorable prognosis and have been suggested to represent independent primary tumors rather than metastatic disease. We subjected sporadic synchronous EECs/EOCs from five patients to whole-exome massively parallel sequencing, which revealed that the EEC and EOC of each case displayed strikingly similar repertoires of somatic mutations and gene copy number alterations. Despite the presence of mutations restricted to the EEC or EOC in each case, we observed that the mutational processes that shaped their respective genomes were consistent. High-depth targeted massively parallel sequencing of sporadic synchronous EECs/EOCs from 17 additional patients confirmed that these lesions are clonally related. In an additional Lynch Syndrome case, however, the EEC and EOC were found to constitute independent cancers lacking somatic mutations in common. Taken together, sporadic synchronous EECs/EOCs are clonally related and likely constitute dissemination from one site to the other. CI - (c) The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. FAU - Schultheis, Anne M AU - Schultheis AM AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Ng, Charlotte K Y AU - Ng CK AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - De Filippo, Maria R AU - De Filippo MR AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Piscuoglio, Salvatore AU - Piscuoglio S AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Macedo, Gabriel S AU - Macedo GS AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Gatius, Sonia AU - Gatius S AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Perez Mies, Belen AU - Perez Mies B AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Soslow, Robert A AU - Soslow RA AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Lim, Raymond S AU - Lim RS AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Viale, Agnes AU - Viale A AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Huberman, Kety H AU - Huberman KH AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Palacios, Jose C AU - Palacios JC AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Reis-Filho, Jorge S AU - Reis-Filho JS AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). FAU - Matias-Guiu, Xavier AU - Matias-Guiu X AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). fjmatiasguiu.lleida.ics@gencat.cat weigeltb@mskcc.org. FAU - Weigelt, Britta AU - Weigelt B AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (AMS, CKYN, MRDF, SP, GSM, RAS, RSL, JSRF, BW); Department of Pathology, Hospital Universitario Arnau de Vilanova, University of Lleida, Lleida, Spain (SG, XMG); Department of Pathology, Hospital Universitario Ramon y Cajal, Madrid, Spain (BPM, JCP); Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY (AV, KHH); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). fjmatiasguiu.lleida.ics@gencat.cat weigeltb@mskcc.org. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - P30CA008748/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160201 PL - United States TA - J Natl Cancer Inst JT - Journal of the National Cancer Institute JID - 7503089 RN - 0 (DNA, Neoplasm) SB - IM CIN - J Natl Cancer Inst. 2016 Jun;108(6):djv442. PMID: 26832772 MH - Carcinoma, Endometrioid/*genetics/pathology MH - Carcinoma, Ovarian Epithelial MH - *Clone Cells MH - Colorectal Neoplasms, Hereditary Nonpolyposis/genetics MH - DNA Mutational Analysis/methods MH - DNA, Neoplasm/*analysis MH - Endometrial Neoplasms/genetics/pathology MH - Exome MH - Female MH - *High-Throughput Nucleotide Sequencing MH - Humans MH - Immunohistochemistry MH - Loss of Heterozygosity MH - Microsatellite Instability MH - Neoplasm Staging MH - Neoplasms, Glandular and Epithelial/*genetics/pathology MH - Neoplasms, Multiple Primary/*genetics/pathology MH - Ovarian Neoplasms/*genetics/pathology PMC - PMC4909128 EDAT- 2016/02/03 06:00 MHDA- 2016/07/13 06:00 PMCR- 2017/06/01 CRDT- 2016/02/03 06:00 PHST- 2015/07/02 00:00 [received] PHST- 2015/12/14 00:00 [accepted] PHST- 2016/02/03 06:00 [entrez] PHST- 2016/02/03 06:00 [pubmed] PHST- 2016/07/13 06:00 [medline] PHST- 2017/06/01 00:00 [pmc-release] AID - djv427 [pii] AID - 10.1093/jnci/djv427 [doi] PST - epublish SO - J Natl Cancer Inst. 2016 Feb 1;108(6):djv427. doi: 10.1093/jnci/djv427. Print 2016 Jun.