title: Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women.
abstract: Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.
authors.affiliation: Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Tony K H
authors.initials: TK
authors.lastname: Chung
authors.affiliation: Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Paul
authors.initials: P
authors.lastname: Van Hummelen
authors.affiliation: Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Chan
authors.affiliation: Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Tak Hong
authors.initials: TH
authors.lastname: Cheung
authors.affiliation: Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: So Fan
authors.initials: SF
authors.lastname: Yim
authors.affiliation: Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Mei Y
authors.initials: MY
authors.lastname: Yu
authors.affiliation: Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Ducar
authors.affiliation: Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Thorner
authors.affiliation: Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: MacConaill
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA.
authors.forename: Graeme
authors.initials: G
authors.lastname: Doran
authors.affiliation: Cancer Program, The Broad Institute of MIT and Harvard University, Cambridge, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Chandra Sekhar
authors.initials: CS
authors.lastname: Pedamallu
authors.affiliation: Cancer Program, The Broad Institute of MIT and Harvard University, Cambridge, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Akinyemi I
authors.initials: AI
authors.lastname: Ojesina
authors.affiliation: Harvard Medical School, Pediatric Surgical Laboratories, Massachusetts General Hospital, Boston, MA.
authors.forename: Raymond R Y
authors.initials: RR
authors.lastname: Wong
authors.affiliation: Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Vivian W
authors.initials: VW
authors.lastname: Wang
authors.affiliation: Cancer Program, The Broad Institute of MIT and Harvard University, Cambridge, MA.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Freeman
authors.affiliation: Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Tat San
authors.initials: TS
authors.lastname: Lau
authors.affiliation: Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kwong
authors.affiliation: Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Loucia K Y
authors.initials: LK
authors.lastname: Chan
authors.affiliation: Division of Psychiatric Genomics, Mount Sinai School of Medicine, New York, NY.
authors.forename: Menachem
authors.initials: M
authors.lastname: Fromer
authors.affiliation: Division of Gynecologic Oncology, Princess Margaret Cancer Center, Toronto, ON, Canada.
authors.forename: Taymaa
authors.initials: T
authors.lastname: May
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Worley
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Esselen
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Elias
authors.affiliation: Cancer Genomics Informatics and Computational Biology, The Broad Institute of Harvard and MIT, Cambridge, MA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lawrence
authors.affiliation: Cancer Genomics Informatics and Computational Biology, The Broad Institute of Harvard and MIT, Cambridge, MA.
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.affiliation: Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN.
authors.forename: David I
authors.initials: DI
authors.lastname: Smith
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Crum
authors.affiliation: Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.|Cancer Program, The Broad Institute of MIT and Harvard University, Cambridge, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Ross S
authors.initials: RS
authors.lastname: Berkowitz
authors.affiliation: Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.|Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Yick Fu
authors.initials: YF
authors.lastname: Wong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000821:virology; D000328:Adult; D000368:Aged; D059472:Exome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006723:Hong Kong; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
keywords: HPV; cervical adenocarcinoma; genomic alternations