Oral oncology · 2026
PTPR family deletions are associated with greater genomic structural instability in young adult tongue cancer.
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Kulkarni Pallavi, Chan Kimberly, Tseng Christopher, Milarachi Emily N, Goldrich David, LaBarge Brandon, Walter Vonn, Goyal Neerav, Curry Joseph M, Linnenbach Alban, Broach James R, Goldenberg David
Аннотация
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 DESIGN: Retrospective cohort study.
SETTING: Tertiary academic medical center.
METHODS: Optical 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.
RESULTS: Mean 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).
CONCLUSION: We found that PTPR family gene deletions, previously implicated in head and neck cancers, may contribute to genomic instability in young OTSCC.
STUDY DESIGN: Retrospective cohort study.
SETTING: Tertiary academic medical center.
METHODS: Optical 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.
RESULTS: Mean 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).
CONCLUSION: We found that PTPR family gene deletions, previously implicated in head and neck cancers, may contribute to genomic instability in young OTSCC.