Integrated genomic and molecular characterization of cervical cancer

被引：1130

作者：

Burk, Robert D. ^{[1
]}

Chen, Zigui ^{[1
]}

Saller, Charles ^{[2
]}

Tarvin, Katherine ^{[2
]}

Carvalho, Andre L. ^{[3
]}

Scapulatempo-Neto, Cristovam ^{[3
]}

Silveira, Henrique C. ^{[3
]}

Fregnani, Jose H. ^{[3
]}

Creighton, Chad J.

Anderson, Matthew L.

Castro, Patricia

Wang, Sophia S. ^{[4
]}

Yau, Christina ^{[5
]}

Benz, Christopher ^{[5
]}

Robertson, A. Gordon ^{[6
]}

Mungall, Karen ^{[6
]}

Lim, Lynette ^{[6
]}

Bowlby, Reanne ^{[6
]}

Sadeghi, Sara ^{[6
]}

Brooks, Denise ^{[6
]}

Sipahimalani, Payal ^{[6
]}

Mar, Richard ^{[6
]}

Ally, Adrian ^{[6
]}

Clarke, Amanda ^{[6
]}

Mungall, Andrew J. ^{[6
]}

Tam, Angela ^{[6
]}

Lee, Darlene ^{[6
]}

Chuah, Eric ^{[6
]}

Schein, Jacqueline E. ^{[6
]}

Tse, Kane ^{[6
]}

Kasaian, Katayoon ^{[6
]}

Ma, Yussanne ^{[6
]}

Marra, Marco A. ^{[6
]}

Mayo, Michael ^{[6
]}

Balasundaram, Miruna ^{[6
]}

Thiessen, Nina ^{[6
]}

Dhalla, Noreen ^{[6
]}

Carlsen, Rebecca ^{[6
]}

Moore, Richard A. ^{[6
]}

Holt, Robert A. ^{[6
]}

Jones, Steven J. M. ^{[6
]}

Wong, Tina ^{[6
]}

Pantazi, Angeliki ^{[7
]}

Parfenov, Michael ^{[7
]}

Kucherlapati, Raju ^{[7
]}

Hadjipanayis, Angela ^{[7
]}

Seidman, Jonathan ^{[7
]}

Kucherlapati, Melanie ^{[7
]}

Ren, Xiaojia ^{[7
]}

Xu, Andrew W. ^{[7
]}

机构：

[1] Albert Einstein Coll Med, Bronx, NY 10461 USA

[2] Analyt Biol Serv Inc, Wilmington, DE 19801 USA

[3] Barretos Canc Hosp, Barretos, SP, Brazil

[4] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA

[5] Buck Inst Res Aging, Novato, CA 94945 USA

[6] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada

[7] Harvard Med Sch, Boston, MA 02115 USA

[8] Christiana Care Hlth Serv Inc, Helen F Graham Canc Ctr, Newark, DE 19713 USA

[9] Christiana Care Hlth Serv Inc, Res Inst, Newark, DE 19713 USA

[10] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA

[11] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA

[12] Univ Alabama Birmingham, Birmingham, AL 35294 USA

[13] ILSbio LLC, Chestertown, MD 21620 USA

[14] Indiana Univ Sch Med, Indianapolis, IN 46202 USA

[15] Inst Human Virol, Abuja, Nigeria

[16] Inst Syst Biol, Seattle, WA 98109 USA

[17] Int Genom Consortium, Phoenix, AZ 85004 USA

[18] Leidos Biomed, Rockville, MD 20850 USA

[19] Massachusetts Gen Hosp, Boston, MA 02114 USA

[20] Washington Univ, McDonnell Genome Inst, St Louis, MO 63108 USA

[21] Med Coll Wisconsin, Milwaukee, WI 53226 USA

[22] Med Univ South Carolina, Charleston, SC 29425 USA

[23] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA

[24] Montefiore Med Ctr, Bronx, NY 10461 USA

[25] NantOmics, Santa Cruz, CA 95060 USA

[26] NCI, Bethesda, MD 20892 USA

[27] Natl Hosp, Abuja, Nigeria

[28] NHGRI, Bethesda, MD 20892 USA

[29] NIEHS, POB 12233, Durham, NC 27709 USA

[30] NIDCD, Bethesda, MD 20892 USA

[31] London Hlth Sci Ctr, Ontario Tumour Bank, London, ON N6A 5A5, Canada

[32] Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada

[33] Ottawa Hosp, Ontario Tumour Bank, Ottawa, ON K1H 8L6, Canada

[34] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[35] Penrose St Francis Hlth Serv, Colorado Springs, CO 80906 USA

[36] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[37] SRA Int, Fairfax, VA 22033 USA

[38] St Josephs Candler Hlth Syst, Savannah, GA 31406 USA

[39] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA

[40] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA

[41] Univ Bergen, Bergen, Norway

[42] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[43] Univ Abuja, Teaching Hosp, Gwagwalada, Abuja, Nigeria

[44] Univ Calif Irvine, Orange, CA 92668 USA

[45] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA

[46] Univ Kansas, Med Ctr, Kansas City, KS 66160 USA

[47] Univ Lausanne, Lausanne, Switzerland

[48] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA

[49] Univ N Carolina, Chapel Hill, NC 27599 USA

[50] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA

来源：

NATURE | 2017年 / 543卷 / 7645期

关键词：

EPITHELIAL-MESENCHYMAL-TRANSITION; TRANSCRIPTION FACTORS; DNA METHYLATION; BREAST-CANCER; 14-3-3-SIGMA; RESISTANCE; EXPRESSION; SIGNATURE; ACCURATE; QUANTIFICATION;

D O I：

10.1038/nature21386

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

引用

页码：378 / +

页数：23

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