TY  - JOUR
TI  - Integrated genomic and molecular characterization of cervical cancer
AU  - Robert D. Burk
AU  - Zigui Chen
AU  - Saller Cf
AU  - Katherine Tarvin
AU  - André L. Carvalho
AU  - Cristovam Scapulatempo-Neto
AU  - Henrique C. Silveira
AU  - José H. Fregnani
AU  - Chad J. Creighton
AU  - Matthew L. Anderson
AU  - Patricia Castro
AU  - Sophia S. Wang
AU  - C Yau
AU  - Christopher Benz
AU  - A. Gordon Robertson
AU  - Karen Mungall
AU  - Lynette Lim
AU  - Reanne Bowlby
AU  - Sara Sadeghi
AU  - Denise Brooks
AU  - Payal Sipahimalani
AU  - Richard Mar
AU  - Ally Ai
AU  - Amanda Clarke
AU  - Andrew J. Mungall
AU  - Angela Tam
AU  - Darlene Lee
AU  - Eric Chuah
AU  - Jacqueline E. Schein
AU  - Kane Tse
AU  - Katayoon Kasaian
AU  - Yussanne Ma
AU  - Marco A. Marra
AU  - Michael Mayo
AU  - Miruna Balasundaram
AU  - Nina Thiessen
AU  - Noreen Dhalla
AU  - Rebecca Carlsen
AU  - Richard A. Moore
AU  - Robert A. Holt
AU  - Steven J.M. Jones
AU  - Tina Wong
AU  - Angeliki Pantazi
AU  - Michael Parfenov
AU  - Raju Kucherlapati
AU  - Angela Hadjipanayis
AU  - J G Seidman
AU  - Melanie Kucherlapati
AU  - Xiaojia Ren
AU  - Andrew W. Xu
AU  - Lixing Yang
AU  - Peter J. Park
AU  - So Lee
AU  - Brenda Rabeno
AU  - Lori Huelsenbeck-Dill
AU  - Mark Borowsky
AU  - Mark Cadungog
AU  - Mary Iacocca
AU  - Nicholas Petrelli
AU  - Patricia Swanson
AU  - Akinyemi I. Ojesina
AU  - Bradley A. Murray
AU  - Hailei Zhang
AU  - Andrew D. Cherniack
AU  - Carrie Sougnez
AU  - Chandra Sekhar Pedamallu
AU  - Lee Lichtenstein
AU  - M. Meyerson
AU  - Michael S. Noble
AU  - David I. Heiman
AU  - Doug Voet
AU  - Getz Gs
AU  - Gordon Saksena
AU  - Jaegil Kim
AU  - Juliann Shih
AU  - Juok Cho
AU  - Michael S. Lawrence
AU  - Nils Gehlenborg
AU  - Pei Lin
AU  - Rameen Beroukhim
AU  - Scott Frazer
AU  - Stacey B. Gabriel
AU  - Steven E. Schumacher
AU  - Xuan Le
AU  - George Sandusky
AU  - Sally N. Adebamowo
AU  - Teniola Akeredolu
AU  - Clement Adebamowo
AU  - Sheila M. Reynolds
AU  - Ilya Shmulevich
AU  - Candace Shelton
AU  - Daniel Crain
AU  - David Mallery
AU  - Erin Curley
AU  - Johanna Gardner
AU  - Robert Penny
AU  - Scott Morris
AU  - Troy Shelton
AU  - J B Liu
AU  - Laxmi Lolla
PY  - 2017
JO  - Nature
DO  - 10.1038/nature21386
UR  - https://doi.org/10.1038/nature21386
AB  - Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers. This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types. Cervical cancer is one of the main causes of cancer-related deaths worldwide, and 95% of cases result from human papilloma virus (HPV) infection. The Cancer Genome Atlas Research Network now reports the genomic and molecular characterization of 228 primary cervical cancers. The authors identify significantly mutated genes and pathways that differ by cervical cancer subtype, and find that keratin-low squamous, keratin-high squamous and adenocarcinoma-rich clusters are marked by different HPV types and molecular features.
ER  -