Human Endogenous Retrovirus Expression Is Associated with Head and Neck Cancer and Differential Survival

Human endogenous retroviruses (HERVs) have been implicated in a variety of human diseases including cancers. However, technical challenges in analyzing HERV sequence data have limited locus-specific characterization of HERV expression. Here, we use the software Telescope (developed to identify expressed transposable elements from metatranscriptomic data) on 43 paired tumor and adjacent normal tissue samples from The Cancer Genome Atlas Program to produce the first locus-specific retrotranscriptome of head and neck cancer. Telescope identified over 3000 expressed HERVs in tumor and adjacent normal tissue, and 1078 HERVs were differentially expressed between the two tissue types. The majority of differentially expressed HERVs were expressed at a higher level in tumor tissue. Differentially expressed HERVs were enriched in members of the HERVH family. Hierarchical clustering based on HERV expression in tumor-adjacent normal tissue resulted in two distinct clusters with significantly different survival probability. Together, these results highlight the importance of future work on the role of HERVs across a range of cancers.

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Photoacoustic Imaging for Measuring Tumors and Normal Tissue in Patients With Head and Neck Cancer

Case Medical Research ◽

10.31525/ct1-nct04110249 ◽

2019 ◽

Author(s):

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Normal Tissue ◽

Photoacoustic Imaging

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Prospective Clinical-dosimetric Evaluation of Normal Tissue Tolerance of the Brachial Plexus among Patients treated by Intensity Modulated Radiotherapy for Head and Neck Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2010.07.377 ◽

2010 ◽

Vol 78 (3) ◽

pp. S152 ◽

Cited By ~ 1

Author(s):

A.M. Chen ◽

D.H. Lau ◽

M. Mathai ◽

W.H. Hall ◽

G. Farwell ◽

...

Keyword(s):

Head And Neck Cancer ◽

Brachial Plexus ◽

Head And Neck ◽

Neck Cancer ◽

Normal Tissue ◽

Intensity Modulated Radiotherapy ◽

Normal Tissue Tolerance ◽

Intensity Modulated

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Comparisons of normal tissue complication probability models derived from planned and delivered dose for head and neck cancer patients

Radiotherapy and Oncology ◽

10.1016/j.radonc.2021.09.015 ◽

2021 ◽

Author(s):

Takahiro Kanehira ◽

Simon van Kranen ◽

Tomas Jansen ◽

Olga Hamming-Vrieze ◽

Abrahim Al-Mamgani ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Normal Tissue ◽

Normal Tissue Complication Probability ◽

Probability Models ◽

Delivered Dose

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3p Arm Loss and Survival in Head and Neck Cancer: An Analysis of TCGA Dataset

Cancers ◽

10.3390/cancers13215313 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5313

Author(s):

Hugh Andrew Jinwook Kim ◽

Mushfiq Hassan Shaikh ◽

Mark Lee ◽

Peter Y. F. Zeng ◽

Alana Sorgini ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Survival Data ◽

Statistical Power ◽

Immune Cell ◽

The Cancer Genome Atlas ◽

Cytokine Signaling ◽

Molecular Characteristics ◽

Chromosome 3P

Loss of the 3p chromosome arm has previously been reported to be a biomarker of poorer outcome in both human papillomavirus (HPV)-positive and HPV-negative head and neck cancer. However, the precise operational measurement of 3p arm loss is unclear and the mutational profile associated with the event has not been thoroughly characterized. We downloaded the clinical, single nucleotide variation (SNV), copy number aberration (CNA), RNA sequencing, and reverse phase protein assay (RPPA) data from The Cancer Genome Atlas (TCGA) and The Cancer Proteome Atlas HNSCC cohorts. Survival data and hypoxia scores were downloaded from published studies. In addition, we report the inclusion of an independent Memorial Sloan Kettering cohort. We assessed the frequency of loci deletions across the 3p arm separately in HPV-positive and -negative disease. We found that deletions on chromosome 3p were almost exclusively an all or none event in the HPV-negative cohort; patients either had <1% or >97% of the arm deleted. 3p arm loss, defined as >97% deletion in HPV-positive patients and >50% in HPV-negative patients, had no impact on survival (p > 0.05). However, HPV-negative tumors with 3p arm loss presented at a higher N-category and overall stage and developed more distant metastases (p < 0.05). They were enriched for SNVs in TP53, and depleted for point mutations in CASP8, HRAS, HLA-A, HUWE1, HLA-B, and COL22A1 (false discovery rate, FDR < 0.05). 3p arm loss was associated with CNAs across the whole genome (FDR < 0.1), and pathway analysis revealed low lymphoid–non-lymphoid cell interactions and cytokine signaling (FDR < 0.1). In the tumor microenvironment, 3p arm lost tumors had low immune cell infiltration (FDR < 0.1) and elevated hypoxia (FDR < 0.1). 3p arm lost tumors had lower abundance of proteins phospho-HER3 and ANXA1, and higher abundance of miRNAs hsa-miR-548k and hsa-miR-421, which were all associated with survival. There were no molecular differences by 3p arm status in HPV-positive patients, at least at our statistical power level. 3p arm loss is largely an all or none phenomenon in HPV-negative disease and does not predict poorer survival from the time of diagnosis in TCGA cohort. However, it produces tumors with distinct molecular characteristics and may represent a clinically useful biomarker to guide treatment decisions for HPV-negative patients.

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