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Data from Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes
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Data from Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes
Data from Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes
LZ
Li Zhang
Li Zhang
KM
Kenzie D. MacIsaac
Kenzie D. MacIsaac
TZ
Ting Zhou
Ting Zhou
PH
Pei-Yu Huang
Pei-Yu Huang
CX
Chunlin Xin
Chunlin Xin
JD
Jason R. Dobson
Jason R. Dobson
KY
Kun Yu
Kun Yu
DC
Derek Y. Chiang
Derek Y. Chiang
YF
Yue Fan
Yue Fan
MP
Marc Pelletier
Marc Pelletier
YW
Yan Wang
Yan Wang
SJ
Savina Jaeger
Savina Jaeger
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3 April 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1541-7786.c.6541285
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.
Keywords
GENE EXPRESSION
TREATMENT
COPY NUMBER
NPC
MUTATIONAL LOAD
LYMPHOCYTE INFILTRATE
LYMPHOCYTES
EBV
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