Genomics

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Gene expression patterns and TP53 mutations are associated with HPV RNA status, lymph node metastasis, and survival in head and neck cancer


ABSTRACT: A growing proportion of head and neck squamous cell carcinomas (HNSCC) is associated with the human papilloma virus (HPV), particularly HPV16. We compare tumors with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited HNSCC patients by gene expression profiling and targeted sequencing of 50 genes. We confirm that the HPV16 DNA+ RNA+ tumors are molecularly distinct from the HPV-negative (DNA-) HNSCC and have elevated expression of cell cycle genes and rare TP53 mutations (3.6%, 1/28). We show that tumors with non-transcriptionally active HPV16 (DNA+ RNA-) are similar to HPV DNA- tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). Furthermore, we identify four gene expression clusters. They moderately but significantly differ in overall survival. One cluster exhibits high expression of immune response genes (IR) and contains most of the HPV16 DNA+ RNA+ patients. The IR cluster and disruptive TP53 mutations are associated with lymph node metastasis independent of HPV16 status and we validate each of these associations in another large data set. Consistent with earlier studies, disruptive TP53 mutations are prognostically unfavorable. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and for the first time identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE65858 | GEO | 2015/06/24

SECONDARY ACCESSION(S): PRJNA275235

REPOSITORIES: GEO

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