PTPR family deletions are associated with greater genomic structural instability in young adult tongue cancer

Objective: Oral tongue squamous cell carcinoma (OTSCC) has traditionally affected older males with tobacco and alcohol exposure. Multiple population-based studies demonstrate a rising trend in OTSCC among younger individuals. Several studies indicate that young adults may experience higher rates of local recurrence and disease relapse. We sought to determine whether variations in somatic structural variants (SVs) and copy number variants (CNVs) could explain differences in clinical outcomes between young and old OTSCC patients.Study DesignRetrospective cohort study.SettingTertiary academic medical center.MethodsOptical genomic mapping (OGM) was performed on DNA isolated from fresh-frozen tumors and whole blood from 8 patients younger than 40 and 13 patients older than 40 to identify tumor-specific SVs. Wilcoxon rank sum tests and contingency table analyses determined statistical significance of differences between old and young tumors.ResultsMean ages of young and old patients were 35.6 ± 4.6 and 71.5 ± 9.2 years, respectively. Young patients were more likely to present with T3/T4 primary tumors (OR = 3.75) undergo chemoradiation (OR = 8.2), and experience recurrence (OR = 7.2). They were less likely to be female (OR: 0.23) and less likely to have tobacco (OR: 0.55) or alcohol use (OR: 0.3). Genomic analysis showed a trend to higher genomic instability and increased aneuploidy in OTSCC from young patients and higher frequencies of PTPR family gene deletions (OR: 2.7), particularly PTPRD (OR: 6.0). Tumors with these gene alterations exhibited significantly more SVs and CNVs (p < 0.05).ConclusionWe found that PTPR family gene deletions, previously implicated in head and neck cancers, may contribute to genomic instability in young OTSCC.