Project description:Purpose: There is substantial heterogeneity within the human papillomavirus (HPV) positive head and neck cancer (HNC) tumors that predispose them to different outcomes, however this subgroup is poorly characterized due to various historical reasons. Experimental Design: we perform unsupervised gene expression clustering on well-annotated HPV(+) HNC samples from two cohorts ( 84 total primary tumors), as well as 18 HPV(-) HNCs, to discover subtypes, and begin to characterize the differences between the subtypes in terms of their HPV characteristics, pathway activity, whole-genome somatic copy number variations and mutation frequencies. Results: We identified two distinctive HPV(+) subtypes by unsupervised clustering. Membership in the HPV(+) subtypes correlates with genic viral integration status, E2/E4/E5 expression levels and the ratio of spliced to full length HPV oncogene E6. The subtypes also show differences in copy number alterations, in particular the loss of chr16q and gain of chr3q, PIK3CA mutation, and in the expression of genes involved in several biological processes related to cancer, including immune response, oxidation-reduction process, and keratinocyte and mesenchymal differentiation. Conclusion: Our characterization of two subtypes of HPV(+) tumors provides valuable molecular level information in relation to the alternative paths to tumor development and to that of HPV(-) HNCs. Together, these results will shed light on stratifications of the HPV(+) HNCs and will help to guide personalized care for HPV(+) HNC patients. 36 head and neck primary tumors (18 HPV+ and 18 HPV-) and their matched blood samples were collected and genotyped by Illumina OmniExpress SNP array. RNA-seq was also performed on the same set of tumor samples.
Project description:Genome wide high resolution assay of copy number in a series of frozen, microdissected head and neck cancers originating from the oral cavity. The objective was to characterize areas of amplification and deletion in head and neck cancers arising from the oral cavity subsite.
Project description:Subtypes of HPV-positive head and neck cancers are associated with HPV characteristics, copy number variations, PIK3CA mutation, and pathway signatures. [SNP]
Project description:Subtypes of HPV-positive head and neck cancers are associated with HPV characteristics, copy number variations, PIK3CA mutation, and pathway signatures. [RNA-Seq]
Project description:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose underlying etiology has not been explained by traditional prognostic factors such as tumor site, stage, or histology. Although previous studies have shown that molecular subtypes of HNSCC exist, the benefit of such a classification scheme has not been fully realized. We show that molecular subtypes of HNSCC exist; that these subtypes have distinct patterns of chromosomal gain and loss, some of which affect canonical oncogenes and tumor suppressors; and that the subtypes are biologically and clinically relevant. These subtypes provide new insight into HNSCC etiology, as well as a valuable method for classifying HNSCC tumors. A total of 141 samples were considered. CEL files were subject to quality control (QC) procedures using the Affymetrix Genotyping Console, and arrays that produced contrast QC measurements above the default threshold of .4 were removed from subsequent analysis. The remaining 99 CEL files were processed with aroma, and log2 intensity ratios were produced using a pooled collection of normal samples as a reference. After segmenting the log2 ratios with DNAcopy, the resulting copy number profiles were subjected to manual review. Arrays that produced low quality copy number profiles were removed from subsequent analysis. Copy number values from chr1 - chr22 were considered.