Squamous Cell Carcinoma of Head and Neck study with SNV (.MAF), WXS data on dbGaP (45 participants)

phs003139 — Genetic Progression of Head and Neck Squamous Cell Carcinoma

These data are tumor/normal-matched exome sequencing results on 45 participants (median age of 58.6 years) treated for squamous cell carcinoma of the oropharynx at <a href="https://www.masseyeandear.org/">Mass Eye and Ear</a> (MEE; Boston, MA, USA). Some tumors had two portions sequenced separately. All research complied with all relevant ethical regulations. Human subject research on patients at <a href="https://www.masseyeandear.org/">MEE</a> was approved by the MEE Human Studies Committee under protocol HSC 11-024H, with informed consent obtained from participants. Participants were not compensated. Clinical data, including HPV status, were abstracted from patient records. Sequencing and clinical data were combined with TCGA data on 486 cases of head and neck squamous cell carcinoma (HNSCC). The PhylogicNDT suite of genomic analysis tools was used to infer the relative timing of genetic events during tumor progression for major molecularly defined classes of HNSCC: HNSCC negative for human papillomavirus (HPV), HPV-associated HNSCC, and HPV-negative HNSCC involving mutations in <a href="https://www.ncbi.nlm.nih.gov/gene/841">CASP8</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/64324">NSD1</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/4851">NOTCH1</a>. The timing of the development of whole-genome somatic events leading to tetraploidy or triploidy and to increased measures of intratumor genetic heterogeneity was determined. Associations of heterogeneity measures with clinical outcomes were assessed. The analysis identified genes with early mutations that likely play roles in HPV-tumor initiation (<a href="https://www.ncbi.nlm.nih.gov/gene/55294">FBXW7</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/4851">NOTCH1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/841">CASP8</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/2195">FAT1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/64324">NSD1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/3265">HRAS</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/2033">EP300</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/1387">CREBBP</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/8085">KMT2D</a>). Genes with mutations at later median relative timing (<a href="https://www.ncbi.nlm.nih.gov/gene/122908712">PK3CA</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/4780">NFE2L2</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/3105">HLA-A</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/23013">SPEN</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/58508">KMT2C</a>) were more likely to be important for progressing to later stages of the disease. Gain of chromosome arm 3q and loss of arm 11q were found to occur more frequent in HPV+ HNSCC cases. A high prevalence of 3p and 17p loss were also observed in HPV+ HNSCC cases.