The landscape of viral expression and host gene fusion and adaptation in human cancer

Tang, Ka-Wei; Alaei-Mahabadi, Babak; Samuelsson, Tore; Lindh, Magnus; Larsson, Erik

doi:10.1038/ncomms3513

Cited by 280 publications

(373 citation statements)

References 46 publications

(61 reference statements)

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“…Considerable proportions of EBV in STAD, HPV in CESC and HNSC, and HBV in liver hepatocellular carcinoma were detected (LIHC; Supplementary Fig. S10), which is consistent with previous reports (10,26). A high proportion of tumors resulting from EBV infection and HPV infection were classified as TMIT I compared with those resulting from HBV infection or those with no virus (84% and 56.4% vs. 18.5% and 35.9%, respectively, P < 0.001; Fig.…”

Section: Oncogenic Virus Infection Is Associated With Tmit Isupporting

confidence: 80%

Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration

Ock

Keam

Kim

et al. 2016

Clinical Cancer Research

224

234

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Purpose: There is currently no reliable biomarker to predict who would benefit from anti-PD-1/PD-L1 inhibitors. We comprehensively analyzed the immunogenomic properties in The Cancer Genome Atlas (TCGA) according to the classification of tumor into four groups based on PD-L1 status and tumor-infiltrating lymphocyte recruitment (TIL), a combination that has been suggested to be a theoretically reliable biomarker of anti-PD-1/PD-L1 inhibitors.Experimental Design: The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (N ¼ 9,677) were analyzed. Based on their median values, the samples were classified into four tumor microenvironment immune types (TMIT). The mutational profiles, PD-L1 amplification, and viral association of the samples were compared according to the four TMITs.Results: The proportions of TMIT I, defined by high PD-L1 and CD8A expression, were high in lung adenocarcinoma (67.1%) and kidney clear cell carcinoma (64.8%) among solid cancers. The number of somatic mutations and the proportion of microsatellite instable-high tumor in TMIT I were significantly higher than those in other TMITs, respectively (P < 0.001). PD-L1 amplification and oncogenic virus infection were significantly associated with TMIT I, respectively (P < 0.001). A multivariate analysis confirmed that the number of somatic mutations, PD-L1 amplification, and Epstein-Barr virus/human papillomavirus infection were independently associated with TMIT I.Conclusions: TMIT I is associated with a high mutational burden, PD-L1 amplification, and oncogenic viral infection. This integrative analysis highlights the importance of the assessment of both PD-L1 expression and TIL recruitment to predict responders to immune checkpoint inhibitors.

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Section: Oncogenic Virus Infection Is Associated With Tmit Isupporting

confidence: 80%

Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration

Ock

Keam

Kim

et al. 2016

Clinical Cancer Research

224

234

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“…42 Additionally, extensive studies from RNA-seq data of more than 3,700 malignant human tumors, including 810 human breast adenocarcinomas, do not support the previous evidence of BLV expression in breast tissue. 43,44 Independent of the lack of conclusive evidence for BLV as a human pathogen, the current concern about BLV should be a good opportunity to address the control and eradication of this prevalent oncogenic retrovirus from cattle herds.…”

Section: Juliarena Et Almentioning

confidence: 99%

Bovine leukemia virus: current perspectives

Juliarena¹,

Barrios²,

Lützelschwab³

et al. 2017

VAAT

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Enzootic bovine leukosis, caused by bovine leukemia virus (BLV), is the most common neoplasm of dairy cattle. Although beef and dairy cattle are susceptible to BLV infection and BLV-associated lymphosarcoma, the disease is more commonly detected in dairy herds, mostly because of the management practices in dairy farms. The pathogenicity of BLV in its natural host, the bovine, depends mainly on the resistance/susceptibility genetics of the animal. The majority of infected cattle are asymptomatic, promoting the extremely high dissemination rate of BLV in many bovine populations. The important productive losses caused by the BLV, added to the health risk of maintaining populations with a high prevalence of infection with a retrovirus, generates the need to implement control measures. Different strategies to control the virus have been attempted. The most effective approach is to identify and cull the totality of infected cattle in the herd. However, this approach is not suitable for herds with high prevalence of infection. At present, no treatment or vaccine has proven effective for the control of BLV. Thus far, the genetic selection of resistant animals emerges as a natural strategy for the containment of the BLV dissemination. In natural conditions, most of the infected, resistant cattle can control the infection, and therefore do not pass the virus to other animals, gradually decreasing the prevalence of the herd.

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“…HPV qPCR was carried out as previously described be Lechner and colleagues (22). HPV-type data for CESC and HNSCC TCGA samples were taken from Tang and colleagues, and based the expression of viral genes in RNA-seq data (21).…”

Section: Hpv Assessmentmentioning

confidence: 99%

Epigenetics Markers of Metastasis and HPV-Induced Tumorigenesis in Penile Cancer

Feber

Arya

Winter

et al. 2015

Clinical Cancer Research

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Purpose: Penile cancer is a rare malignancy in the developed world with just more than 1,600 new cases diagnosed in the United States per year; however, the incidence is much higher in developing countries. Although HPV is known to contribute to tumorigenesis, little is known about the genetic or epigenetic alterations defining penile cancer.Experimental Design: Using high-density genome-wide methylation arrays, we have identified epigenetic alterations associated with penile cancer. Q-MSP was used to validate lymph node metastasis markers in 50 cases. A total of 446 head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESCC) samples were used to validate HPV-associated epigenetic alterations.Results: We defined 6,933 methylation variable positions (MVP) between normal and tumor tissue, which includes 997 hypermethylated differentially methylated regions associated with tumor supressor genes, including CDO1, AR1, and WT1. Analysis of penile cancer tumors identified a 4 gene episignature which accurately predicted lymph node metastasis in an independent cohort (AUC of 89%). Finally, we explored the epigenetic alterations associated with penile cancer HPV infection and defined a 30 loci lineage-independent HPV specific epi-signature which predicts HPV status and survival in independent HNSCC, CESC cohorts. Epi-signature-negative patients have a significantly worse overall survival [HNSCC P ¼ 0.00073; 95% confidence interval (CI), 0.021-0.78; CESC P ¼ 0.0094; HR ¼ 3.91, 95% CI ¼ 0.13-0.78], HPV epi-signature is a better predictor of survival than HPV status alone.Conclusions: These data demonstrate for the first time genome-wide epigenetic events involved in an aggressive penile cancer phenotype and define the epigenetic alterations common across multiple HPV-driven malignancies.

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The landscape of viral expression and host gene fusion and adaptation in human cancer

Cited by 280 publications

References 46 publications

Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration

Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration

Bovine leukemia virus: current perspectives

Epigenetics Markers of Metastasis and HPV-Induced Tumorigenesis in Penile Cancer

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