The genomic landscape of nasopharyngeal carcinoma

被引：307

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：

新加坡国家研究基金会; 英国医学研究理事会; 美国国家卫生研究院;

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

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