GRCh38 · COSMIC v99

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Reference

Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-based Subtypes.

Paper ID

COSP44189

Authors

Zhang L, MacIsaac KD, Zhou T, Huang PY, Xin C, Dobson JR, Yu K, Chiang DY, Fan Y, Pelletier MR, Wang Y, Jaeger S, Krishnamurthy Radhakrishna V, JeBailey L, Skewes-Cox P, Zhang J, Fang W, Huang Y, Zhao H, Zhao Y, Li E, Peng B, Huang A, Dranoff G, Hammerman PS, Engelman JA, Bitter H, Zeng YX and Yao Y

Affiliation

State Key Laboratory of Oncology in South China, and Department of Medical Oncology, Sun Yat-Sen University Cancer Center.

Journal

Molecular cancer research : MCR, 2017
ISSN: 1557-3125
PMID: 28851814 (view at PubMed or Europe PMC)

Abstract

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated cancer characterized by a poor prognosis and a high level of lymphocyte infiltrate. Genetic hallmarks of NPC are not completely known but include deletion of the p16 (CDKN2A) locus and mutations in NF-kB pathway components, with a relatively low total mutational load. To better understand the genetic landscape, an integrated genomic analysis was performed using a large clinical cohort of treatment-naïve NPC tumor specimens. This genomic analysis was generally concordant with previous studies; however, three subtypes of NPC were identified by differences in immune cell gene expression, prognosis, tumor cell morphology, and genetic characteristics. A gene expression signature of proliferation was poorly prognostic and associated with either higher mutation load or specific EBV gene expression patterns in a subtype-specific manner. Finally, higher levels of stromal tumor-infiltrating lymphocytes associated with good prognosis and lower expression of a WNT and TGF-beta pathway activation signature.Implications: This study represents the first integrated analysis of mutation, copy number, and gene expression data in NPC and suggests how tumor genetics and EBV infection influence the tumor microenvironment (TME) in this disease. These insights should be considered for guiding immunotherapy treatment strategies in this disease.

Paper Status

Curated