title: Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas.
abstract: 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.
authors.affiliation: 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 Ramón 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).
authors.forename: Anne M
authors.initials: AM
authors.lastname: Schultheis
authors.affiliation: 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 Ramón 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).
authors.forename: Charlotte K Y
authors.initials: CK
authors.lastname: Ng
authors.affiliation: 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 Ramón 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).
authors.forename: Maria R
authors.initials: MR
authors.lastname: De Filippo
authors.affiliation: 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 Ramón 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).
authors.forename: Salvatore
authors.initials: S
authors.lastname: Piscuoglio
authors.affiliation: 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 Ramón 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).
authors.forename: Gabriel S
authors.initials: GS
authors.lastname: Macedo
authors.affiliation: 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 Ramón 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).
authors.forename: Sonia
authors.initials: S
authors.lastname: Gatius
authors.affiliation: 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 Ramón 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).
authors.forename: Belen
authors.initials: B
authors.lastname: Perez Mies
authors.affiliation: 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 Ramón 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).
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.affiliation: 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 Ramón 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).
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Lim
authors.affiliation: 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 Ramón 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).
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.affiliation: 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 Ramón 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).
authors.forename: Kety H
authors.initials: KH
authors.lastname: Huberman
authors.affiliation: 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 Ramón 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).
authors.forename: Jose C
authors.initials: JC
authors.lastname: Palacios
authors.affiliation: 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 Ramón 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).
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.affiliation: 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 Ramón 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.
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.affiliation: 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 Ramón 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.
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
mesh_terms: D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D002999:Clone Cells; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000032:analysis*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology; D059472:Exome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D053842:Microsatellite Instability; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm
references.citation: Int J Gynaecol Obstet. 2014 Jan;124(1):1-5
references.pmid: 24219974
references.citation: Int J Gynaecol Obstet. 2014 May;125(2):97-8
references.pmid: 24630859
references.citation: Nat Genet. 2014 Nov;46(11):1166-9
references.pmid: 25240283
references.citation: Nat Med. 2015 Jul;21(7):751-9
references.pmid: 26099045
references.citation: Diagn Mol Pathol. 2001 Jun;10(2):116-22
references.pmid: 11385321
references.citation: J Pathol. 2011 Apr;223(5):567-73
references.pmid: 21381030
references.citation: Clin Cancer Res. 2008 Sep 15;14(18):5840-8
references.pmid: 18794095
references.citation: Ann Diagn Pathol. 2012 Aug;16(4):312-4
references.pmid: 22417864
references.citation: Hum Pathol. 2005 Jun;36(6):605-19
references.pmid: 16021566
references.citation: PLoS Med. 2015 Feb 24;12(2):e1001789
references.pmid: 25710373
references.citation: Mod Pathol. 2014 Jan;27(1):128-34
references.pmid: 23765252
references.citation: Nature. 2010 Apr 15;464(7291):999-1005
references.pmid: 20393555
references.citation: Nature. 2014 Jan 23;505(7484):495-501
references.pmid: 24390350
references.citation: Nat Genet. 2015 Mar;47(3):257-62
references.pmid: 25642631
references.citation: Gynecol Oncol. 2004 Aug;94(2):456-62
references.pmid: 15297188
references.citation: J Gynecol Oncol. 2011 Dec;22(4):239-43
references.pmid: 22247800
references.citation: N Engl J Med. 2012 Mar 8;366(10):883-92
references.pmid: 22397650
references.citation: J Mol Diagn. 2015 May;17(3):251-64
references.pmid: 25801821
references.citation: Genome Res. 2012 Feb;22(2):196-207
references.pmid: 22183965
references.citation: J Natl Cancer Inst. 2016 Feb 01;108(6):djv428
references.pmid: 26832771
references.citation: Cancer. 1982 Jul 1;50(1):163-70
references.pmid: 7083121
references.citation: Hum Pathol. 2004 Nov;35(11):1360-8
references.pmid: 15668893
references.citation: Science. 2014 Oct 10;346(6206):251-6
references.pmid: 25301630
references.citation: Nature. 2013 Aug 22;500(7463):415-21
references.pmid: 23945592
references.citation: Int J Gynecol Cancer. 2008 Jan-Feb;18(1):159-64
references.pmid: 17506847
references.citation: Nature. 2013 Oct 17;502(7471):333-9
references.pmid: 24132290
references.citation: Nature. 2013 May 2;497(7447):67-73
references.pmid: 23636398
references.citation: Obstet Gynecol. 2009 Apr;113(4):783-9
references.pmid: 19305320
references.citation: Nat Rev Genet. 2014 Sep;15(9):585-98
references.pmid: 24981601
references.citation: Arch Gynecol Obstet. 2012 Mar;285(3):817-21
references.pmid: 21842403
references.citation: Cancer Discov. 2015 Aug;5(8):821-31
references.pmid: 26003801
references.citation: Hum Pathol. 2005 Jun;36(6):597-9
references.pmid: 16021564
references.citation: Cancer. 1995 Jan 1;75(1):81-6
references.pmid: 7804981
references.citation: Mod Pathol. 2015 Aug;28(8):1101-22
references.pmid: 26089092
references.citation: Int J Gynecol Pathol. 2002 Jul;21(3):205-11
references.pmid: 12068164
references.citation: Gynecol Oncol. 2001 Nov;83(2):355-62
references.pmid: 11606097
references.citation: Cancer. 1991 Dec 1;68(11):2455-9
references.pmid: 1933783
references.citation: Hum Pathol. 1985 Jan;16(1):28-34
references.pmid: 2982713
references.citation: Nat Rev Cancer. 2004 Mar;4(3):177-83
references.pmid: 14993899
references.citation: J Pathol. 2015 Oct;237(2):166-78
references.pmid: 26011570