title: The genomic landscape of nasopharyngeal carcinoma.
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.
authors: 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].
authors: De-Chen
authors: DC
authors: Lin
authors: 1] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [2] Department of Medicine, School of Medicine, National University of Singapore, Singapore. [3].
authors: Xuan
authors: X
authors: Meng
authors: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors: Masaharu
authors: M
authors: Hazawa
authors: 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.
authors: Yasunobu
authors: Y
authors: Nagata
authors: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors: Ana Maria
authors: AM
authors: Varela
authors: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors: Liang
authors: L
authors: Xu
authors: 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.
authors: Yusuke
authors: Y
authors: Sato
authors: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors: Li-Zhen
authors: LZ
authors: Liu
authors: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors: Ling-Wen
authors: LW
authors: Ding
authors: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors: Arjun
authors: A
authors: Sharma
authors: 1] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [2] Department of Haematology-Oncology, National University Cancer Institute, Singapore.
authors: Boon Cher
authors: BC
authors: Goh
authors: 1] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [2] Department of Haematology-Oncology, National University Cancer Institute, Singapore.
authors: Soo Chin
authors: SC
authors: Lee
authors: Department of Pathology, National University Health System, Singapore.
authors: Bengt Fredrik
authors: BF
authors: Petersson
authors: Department of Otolaryngology, National University Hospital Singapore, Singapore.
authors: Feng Gang
authors: FG
authors: Yu
authors: Department of Immunology, National University of Singapore, Singapore.
authors: Paul
authors: P
authors: Macary
authors: Department of Immunology, National University of Singapore, Singapore.
authors: Min Zin
authors: MZ
authors: Oo
authors: Department of Microbiology, National University of Singapore, Singapore.
authors: Chan Soh
authors: CS
authors: Ha
authors: 1] Cancer Science Institute of Singapore, National University of Singapore, Singapore. [2].
authors: Henry
authors: H
authors: Yang
authors: 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].
authors: Seishi
authors: S
authors: Ogawa
authors: 1] Department of Otolaryngology, National University Hospital Singapore, Singapore. [2].
authors: Kwok Seng
authors: KS
authors: Loh
authors: 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].
authors: H Phillip
authors: HP
authors: Koeffler
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D002277:Carcinoma; D002460:Cell Line; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics; D059472:Exome; D023281:Genomics / Q000379:methods; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics
chemical_list: D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors