Genomics and Proteomics of Head and Neck Cancer

National Institute On Deafness And Other Communication Disorders

Investigators

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Abstract

Next generation RNA and DNA sequencing of HNSCC has been undertaken to identify important genetic and microRNA drivers that regulate broader changes in gene expression and malignant phenotype. We have contributed to identification of significantly decreased microRNAs and upregulated target RNAs from data from 279 HNSCC tumors as part of The Cancer Genome Atlas (TCGA) head and neck cancer group (TCGA, Nature, 2015). We have completed a comprehensive genomic and proteomic analysis and comparison of 1409 head and neck, lung, esophageal, cervical, and bladder squamous cell carcinomas (Cell Reports, 2018). These studies identify common and distinguishing molecular features of these cancers. We have completed comprehensive RNA, microRNA and exome sequencing of a large panel of HNSCC cell lines, to identify key mutations, and alterations in copy number, mRNA and miRNA that define models refective of tumor subsets for functional and therapeutic analysis. Studies in HNSCC cell lines confirm important roles for several of these genes, and candidate therapeutics demonstrating in vitro and in vivo activity in preclinical models. We have identified a candidate family of miRNAs whose decrease contributes to the increased expression of genes in HNSCC. Recent studies have focused on the inflammatory transcriptome regulated by co-activation of the classical and alternative NF-kB pathways, and functional RNAi screen of genes mediating aberrant and TNFalpha induced activation of NF-kB in HNSCC.