Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA+ RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). We also find that an immune response-related gene expression cluster is associated with lymph node metastasis, independent of HPV16 status and that disruptive TP53 mutations are associated with lymph node metastasis in HPV16 DNA- tumors. We validate each of these associations in another large data set. Four gene expression clusters which we identify differ moderately but significantly in overall survival. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC.
PubMed ID: 26095926
Projects: LIFE Head and Neck Cancer Group
Journal: Int J Cancer
Human Diseases: Head and neck cancer
Citation: Int J Cancer. 2015 Dec 15;137(12):2846-57. doi: 10.1002/ijc.29649. Epub 2015 Jul 6.
Date Published: 15th Dec 2015
Authors: G. Wichmann, Maciej Rosolowski, K. Krohn, Markus Kreuz, A. Boehm, A. Reiche, U. Scharrer, D. Halama, J. Bertolini, U. Bauer, D. Holzinger, M. Pawlita, J. Hess, Christoph Engel, D. Hasenclever, Markus Scholz, P. Ahnert, Toralf Kirsten, A. Hemprich, C. Wittekind, O. Herbarth, F. Horn, A. Dietz, Markus Löffler
Created: 25th Apr 2019 at 12:24
Last updated: 21st Oct 2019 at 08:57