The genomic landscape of nasopharyngeal carcinoma

被引：298

作者：

Lin, De-Chen ^{[1
,2
]}

Meng, Xuan ^{[1
,3
]}

Hazawa, Masaharu ^{[1
]}

Nagata, Yasunobu ^{[4
,5
]}

Varela, Ana Maria ^{[1
]}

Xu, Liang ^{[1
]}

Sato, Yusuke ^{[4
,5
]}

Liu, Li-Zhen ^{[1
]}

Ding, Ling-Wen ^{[1
]}

Sharma, Arjun ^{[1
]}

Goh, Boon Cher ^{[1
,6
]}

Lee, Soo Chin ^{[1
,6
]}

Petersson, Bengt Fredrik ^{[7
]}

Yu, Feng Gang ^{[8
]}

Macary, Paul ^{[9
]}

Oo, Min Zin ^{[9
]}

Ha, Chan Soh ^{[10
]}

Yang, Henry ^{[1
]}

Ogawa, Seishi ^{[4
,5
]}

Loh, Kwok Seng ^{[8
]}

Koeffler, H. Phillip ^{[1
,2
,11
]}

机构：

[1] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore

[2] Univ Calif Los Angeles, Los Angeles Sch Med, Div Hematol Oncol, Cedars Sinai Med Ctr, Los Angeles, CA USA

[3] Natl Univ Singapore, Sch Med, Dept Med, Singapore 117548, Singapore

[4] Univ Tokyo, Grad Sch Med, Canc Genom Project, Tokyo, Japan

[5] Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan

[6] Natl Univ Canc Inst, Dept Haematol Oncol, Singapore, Singapore

[7] Natl Univ Hlth Syst, Dept Pathol, Singapore, Singapore

[8] Natl Univ Singapore Hosp, Dept Otolaryngol, Singapore 117548, Singapore

[9] Natl Univ Singapore, Dept Immunol, Singapore 117548, Singapore

[10] Natl Univ Singapore, Dept Microbiol, Singapore 117548, Singapore

[11] Natl Univ Singapore Hosp, Natl Univ Canc Inst, Singapore 117548, Singapore

来源：

NATURE GENETICS | 2014年 / 46卷 / 08期

基金：

美国国家卫生研究院; 英国医学研究理事会; 新加坡国家研究基金会;

关键词：

HIGH-THROUGHPUT ANNOTATION; INACTIVATING MUTATIONS; TARGETING AUTOPHAGY; SOMATIC MUTATIONS; TUMOR-SUPPRESSOR; ARID1A MUTATIONS; P53; GENE; CANCER; REVEALS; MUTAGENESIS;

D O I：

10.1038/ng.3006

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Nasopharyngeal carcinoma (NPC) has extremely skewed ethnic and geographic distributions, is poorly understood at the genetic level and is in need of effective therapeutic approaches. Here we determined the mutational landscape of 128 cases with NPC using whole-exome and targeted deep sequencing, as well as SNP array analysis. These approaches revealed a distinct mutational signature and nine significantly mutated genes, many of which have not been implicated previously in NPC. Notably, integrated analysis showed enrichment of genetic lesions affecting several important cellular processes and pathways, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Further functional studies suggested the biological relevance of these lesions to the NPC malignant phenotype. In addition, we uncovered a number of new druggable candidates because of their genomic alterations. Together our study provides a molecular basis for a comprehensive understanding of, and exploring new therapies for, NPC.

引用

页码：866 / 871

页数：6

共 51 条

[1] A method and server for predicting damaging missense mutations
Adzhubei, Ivan A.
Schmidt, Steffen
Peshkin, Leonid
Ramensky, Vasily E.
Gerasimova, Anna
Bork, Peer
Kondrashov, Alexey S.
Sunyaev, Shamil R.
[J]. NATURE METHODS, 2010, 7 (04) : 248 - 249
[2] Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1
Agrawal, Nishant
Frederick, Mitchell J.
Pickering, Curtis R.
Bettegowda, Chetan
Chang, Kyle
Li, Ryan J.
Fakhry, Carole
Xie, Tong-Xin
Zhang, Jiexin
Wang, Jing
Zhang, Nianxiang
El-Naggar, Adel K.
Jasser, Samar A.
Weinstein, John N.
Trevino, Lisa
Drummond, Jennifer A.
Muzny, Donna M.
Wu, Yuanqing
Wood, Laura D.
Hruban, Ralph H.
Westra, William H.
Koch, Wayne M.
Califano, Joseph A.
Gibbs, Richard A.
Sidransky, David
Vogelstein, Bert
Velculescu, Victor E.
Papadopoulos, Nickolas
Wheeler, David A.
Kinzler, Kenneth W.
Myers, Jeffrey N.
[J]. SCIENCE, 2011, 333 (6046) : 1154 - 1157
[3] Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma
Amaravadi, Ravi K.
Yu, Duonan
Lum, Julian J.
Bui, Thi
Christophorou, Maria A.
Evan, Gerard I.
Thomas-Tikhonenko, Andrei
Thompson, Craig B.
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (02) : 326 - 336
[4] Principles and Current Strategies for Targeting Autophagy for Cancer Treatment
Amaravadi, Ravi K.
Lippincott-Schwartz, Jennifer
Yin, Xiao-Ming
Weiss, William A.
Takebe, Naoko
Timmer, William
DiPaola, Robert S.
Lotze, Michael T.
White, Eileen
[J]. CLINICAL CANCER RESEARCH, 2011, 17 (04) : 654 - 666
[5] RELATIONSHIP BETWEEN EPSTEIN-BARR VIRUS AND UNDIFFERENTIATED NASOPHARYNGEAL CARCINOMA - CORRELATED NUCLEIC-ACID HYBRIDIZATION AND HISTOPATHOLOGICAL EXAMINATION
ANDERSSONANVRET, M
FORSBY, N
KLEIN, G
HENLE, W
[J]. INTERNATIONAL JOURNAL OF CANCER, 1977, 20 (04) : 486 - 494
[6] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci
Bei, Jin-Xin
Li, Yi
Jia, Wei-Hua
Feng, Bing-Jian
Zhou, Gangqiao
Chen, Li-Zhen
Feng, Qi-Sheng
Low, Hui-Qi
Zhang, Hongxing
He, Fuchu
Tai, E. Shyong
Kang, Tiebang
Liu, Edison T.
Liu, Jianjun
Zeng, Yi-Xin
[J]. NATURE GENETICS, 2010, 42 (07) : 599 - U173
[7] Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells
Bellodi, Cristian
Lidonnici, Maria Rosa
Hamilton, Ashley
Helgason, G. Vignir
Soliera, Angela Rachele
Ronchetti, Mattia
Galavotti, Sara
Young, Kenneth W.
Selmi, Tommaso
Yacobi, Rinat
Van Etten, Richard A.
Donato, Nick
Hunter, Ann
Dinsdale, David
Tirro, Elena
Vigneri, Paolo
Nicotera, Pierluigi
Dyer, Martin J.
Holyoake, Tessa
Salomoni, Paolo
Calabretta, Bruno
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (05) : 1109 - 1123
[8] Evidence for APOBEC3B mutagenesis in multiple human cancers
Burns, Michael B.
Temiz, Nuri A.
Harris, Reuben S.
[J]. NATURE GENETICS, 2013, 45 (09) : 977 - +
[9] APOBEC3B is an enzymatic source of mutation in breast cancer
Burns, Michael B.
Lackey, Lela
Carpenter, Michael A.
Rathore, Anurag
Land, Allison M.
Leonard, Brandon
Refsland, Eric W.
Kotandeniya, Delshanee
Tretyakova, Natalia
Nikas, Jason B.
Yee, Douglas
Temiz, Nuri I. A.
Donohue, Duncan E.
McDougle, Rebecca M.
Brown, William L.
Law, Emily K.
Harris, Reuben S.
[J]. NATURE, 2013, 494 (7437) : 366 - 370
[10] Prioritization of driver mutations in pancreatic cancer using cancer-specific high-throughput annotation of somatic mutations (CHASM)
Carter, Hannah
Samayoa, Josue
Hruban, Ralph H.
Karchin, Rachel
[J]. CANCER BIOLOGY & THERAPY, 2010, 10 (06) : 582 - 587

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