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Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes.
- Source :
-
Molecular cancer research : MCR [Mol Cancer Res] 2017 Dec; Vol. 15 (12), pp. 1722-1732. Date of Electronic Publication: 2017 Aug 29. - Publication Year :
- 2017
-
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-κB 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 TGFβ 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 in this disease. These insights should be considered for guiding immunotherapy treatment strategies in this disease. Mol Cancer Res; 15(12); 1722-32. ©2017 AACR .<br /> (©2017 American Association for Cancer Research.)
- Subjects :
- Adult
Aged
Carcinoma pathology
Carcinoma virology
Cell Proliferation genetics
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p18 genetics
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Genomics
Herpesvirus 4, Human genetics
Herpesvirus 4, Human pathogenicity
Humans
Lymphocytes, Tumor-Infiltrating metabolism
Lymphocytes, Tumor-Infiltrating pathology
Male
Middle Aged
Mutation
NF-kappa B genetics
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms pathology
Nasopharyngeal Neoplasms virology
Transforming Growth Factor beta genetics
Wnt Signaling Pathway genetics
Carcinoma genetics
Genome, Human genetics
Nasopharyngeal Neoplasms genetics
Prognosis
Tumor Microenvironment genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3125
- Volume :
- 15
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Molecular cancer research : MCR
- Publication Type :
- Academic Journal
- Accession number :
- 28851814
- Full Text :
- https://doi.org/10.1158/1541-7786.MCR-17-0134