The genomic landscape of nasopharyngeal carcinoma

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics
  • Carcinoma
  • Cell Line
  • Cell Line, Tumor
  • ErbB Receptors / genetics
  • Exome
  • Genomics / methods
  • HEK293 Cells
  • Heterografts
  • Humans
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / enzymology
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology
  • Phenotype
  • Phosphatidylinositol 3-Kinases / genetics
  • Polymorphism, Single Nucleotide
  • Signal Transduction / genetics


  • Phosphatidylinositol 3-Kinases
  • EGFR protein, human
  • ErbB Receptors

Associated data

  • GEO/GSE57100
  • SRA/SRP035573