Genome-Wide Profiling of Acquired Uniparental Disomy Reveals Prognostic Factors in Head and Neck Squamous Cell Carcinoma

Acquired uniparental disomy (aUPD) leads to homozygosity facilitating identification of monoallelically expressed genes. We analyzed single-nucleotide polymorphism array-based genotyping data of 448 head and neck squamous cell carcinoma (HNSCC) samples from The Cancer Genome Atlas to determine the frequency and distribution of aUPD regions and their association with survival, as well as to gain a better understanding of their influence on the tumor genome. We used expression data from the same dataset to identify differentially expressed genes between groups with and without aUPD. Univariate and multivariable Cox proportional hazards models were performed for survival analysis. We found that 82.14% of HNSCC samples carried aUPD; the most common regions were in chromosome 17p (31.25%), 9p (30.13%), and 9q (27.46%). In univariate analysis, five independent aUPD regions at chromosome 9p, two regions at chromosome 9q, and the CDKN2A region were associated with poor overall survival in all groups, including training and test sets and human papillomavirus (HPV)-negative samples. Forty-three genes in areas of aUPD including PD-L1 and CDKN2A were differentially expressed in samples with aUPD compared to samples without aUPD. In multivariable analysis, aUPD at the CDKN2A region was a significant predictor of overall survival in the whole cohort and in patients with HPV-negative HNSCC. aUPD at specific regions in the genome influences clinical outcomes of HNSCC and may be beneficial for selection of personalized therapy to prolong survival in patients with this disease.