The Landscape of Somatic Copy Number Alterations in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Somatic copy number alterations (CNAs) play a significant role in the development of this lethal cancer. In this study, we present a meta-analysis of CNAs for a total of 1,395 HNSCC samples. Publicly available R packages and in-house scripts were used for genomic array data processing, including normalization, segmentation and CNA calling. We detected 125 regions of significant gains or losses using GISTIC algorithm and found several potential driver genes in these regions. The incidence of chromothripsis in HNSCC was estimated to be 6%, and the chromosome pulverization hotspot regions were detected. We determined 323 genomic locations significantly enriched for breakpoints, which indicate HNSCC-specific genomic instability regions. Unsupervised clustering of genome-wide CNA data revealed a sub-cluster predominantly composed of nasopharynx tumors and presented a large proportion of HPV-positive samples. These results will facilitate the discovery of therapeutic candidates and extend our molecular understanding of HNSCC.