TY - JOUR
T1 - Integrated genomic and molecular characterization of cervical cancer
AU - The Cancer Genome Atlas Research Network
AU - Burk, Robert D.
AU - Chen, Zigui
AU - Saller, Charles
AU - Tarvin, Katherine
AU - Carvalho, Andre L.
AU - Scapulatempo-Neto, Cristovam
AU - Silveira, Henrique C.
AU - Fregnani, José H.
AU - Creighton, Chad J.
AU - Anderson, Matthew L.
AU - Castro, Patricia
AU - Wang, Sophia S.
AU - Yau, Christina
AU - Benz, Christopher
AU - Gordon Robertson, A.
AU - Mungall, Karen
AU - Lim, Lynette
AU - Bowlby, Reanne
AU - Sadeghi, Sara
AU - Brooks, Denise
AU - Sipahimalani, Payal
AU - Mar, Richard
AU - Ally, Adrian
AU - Clarke, Amanda
AU - Mungall, Andrew J.
AU - Tam, Angela
AU - Lee, Darlene
AU - Chuah, Eric
AU - Schein, Jacqueline E.
AU - Tse, Kane
AU - Kasaian, Katayoon
AU - Ma, Yussanne
AU - Marra, Marco A.
AU - Mayo, Michael
AU - Balasundaram, Miruna
AU - Thiessen, Nina
AU - Dhalla, Noreen
AU - Carlsen, Rebecca
AU - Moore, Richard A.
AU - Holt, Robert A.
AU - Jones, Steven J.M.
AU - Wong, Tina
AU - Pantazi, Angeliki
AU - Parfenov, Michael
AU - Kucherlapati, Raju
AU - Hadjipanayis, Angela
AU - Seidman, Jonathan
AU - Kucherlapati, Melanie
AU - Ren, Xiaojia
AU - Borowsky, Mark
N1 - Publisher Copyright:
© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2017/3/16
Y1 - 2017/3/16
N2 - 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.
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.
UR - https://www.scopus.com/pages/publications/85016138846
U2 - 10.1038/nature21386
DO - 10.1038/nature21386
M3 - Article
C2 - 28112728
AN - SCOPUS:85016138846
SN - 0028-0836
VL - 543
SP - 378
EP - 384
JO - Nature
JF - Nature
IS - 7645
ER -
SDG 3 Good Health and Well-being