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Nat Genet. 2014 Aug;46(8):866-71. doi: 10.1038/ng.3006. Epub 2014 Jun 22.

The genomic landscape of nasopharyngeal carcinoma.

Author information

1
1] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [2] Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine, Los Angeles, California, USA. [3].
2
1] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [2] Department of Medicine, School of Medicine, National University of Singapore, Singapore. [3].
3
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
4
1] Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. [2] Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
5
1] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [2] Department of Haematology-Oncology, National University Cancer Institute, Singapore.
6
Department of Pathology, National University Health System, Singapore.
7
Department of Otolaryngology, National University Hospital Singapore, Singapore.
8
Department of Immunology, National University of Singapore, Singapore.
9
Department of Microbiology, National University of Singapore, Singapore.
10
1] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [2].
11
1] Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. [2] Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. [3].
12
1] Department of Otolaryngology, National University Hospital Singapore, Singapore. [2].
13
1] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [2] Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine, Los Angeles, California, USA. [3] National University Cancer Institute, National University Hospital Singapore, Singapore. [4].

Abstract

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.

PMID:
24952746
DOI:
10.1038/ng.3006
[Indexed for MEDLINE]

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