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Abstract <p>Oral squamous cell carcinoma (OSCC) in young adults is an aggressive and rapidly progressive disease that is not correlated with traditional risk factors such as smoking, alcohol consumption, or human papillomavirus (HPV) infection. The aim of the study was to identify genetic alterations associated with early-onset OSCC progression. The study included 25 young patients with OSCC living in the Russian Federation. Whole-exome sequencing of primary tumor and peripheral blood samples was performed using the SureSelect XT v. 8.0 DNA library preparation kit on the Genolab M platform. Analysis of single nucleotide variants (SNVs) and insertions and deletions (indels) was performed using the GATK pipeline; filtering of genetic variants in the tumor relative to those in the peripheral blood was performed using the Mutect2 pipeline; mutation annotation was performed using ANNOVAR. Statistical data processing was performed using the IBM SPSS Statistics 20 software package. To test mutations that showed a statistically significant result in relation to relapse-free, metastasis-free, and overall survival, data from the Cancer Genome Atlas (<i>N</i> = 127) were used. There was revealed the prognostic significance of somatic mutations in the <i>TAF1L</i>, <i>CUL7</i>, <i>PRPS1L1</i>, and <i>CDKN2A</i> genes for relapse-free survival (<i>p</i> = 0.003, <i>p</i> = 0.003, <i>p</i> = 0.003, and <i>p</i> = 0.004 respectively), <i>PLEC</i> and <i>TEP1</i> for metastasis-free survival (<i>p</i> &lt; 0.001 and <i>p</i> = 0.007 respectively), and <i>ADGRL3</i>, <i>PREX1</i>, and <i>CDKN2A</i> for overall survival (<i>p</i> = 0.023, <i>p</i> = 0.023, and <i>p</i> &lt; 0.001 respectively). All mutations in the <i>CDKN2A</i> gene were frameshift or resulted in a premature termination codon; one patient was found to have a pathogenic variant rs121913387. For the <i>CUL7</i> gene, the variant rs369167170 was recurrent in patients with relapses, and for the <i>PLEC</i> gene, the variant in the region 7:18027430 C&gt;A was recurrent in patients with metastases. Analysis of the data from The Cancer Genome Atlas confirmed the association of only mutations of <i>CDKN2A</i> with OSCC progression at the age of 45 years (<i>N</i> = 18, <i>p</i> = 0.049), but not in older patients (<i>N</i> = 109). This work revealed genetic alterations associated with the progression of early-onset OSCC, which require confirmation of their significance in a larger sample of patients and an assessment of their functional significance.</p>

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Genetic Alterations of Oral Cancer Associated with Progression in Young Adults

  • 期刊论文

  • 发表日期：

    2025年5月1日

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  • E. S. Kolegova,
  • A. A. Korobeynikova,
  • R. S. Vorobev,
  • I. K. Fedorova,
  • D. E. Kulbakin,
  • G. A. Kononova,
  • L. D. Zhuikova,
  • A. P. Polyakov,
  • A. V. Mordovsky,
  • I. V. Novikova,
  • A. D. Kaprin,
  • P. A. Shatalov,
  • P. V. Shegai,
  • L. P. Yakovleva,
  • A. S. Vyalov,
  • V. T. Tsiklauri,
  • O. A. Saprina,
  • M. A. Kropotov,
  • N. G. Suchkova,
  • N. S. Sukortseva,
  • S. I. Samoilova,
  • I. V. Reshetov,
  • E. L. Choinzonov,
  • E. V. Denisov

摘要

Abstract

Oral squamous cell carcinoma (OSCC) in young adults is an aggressive and rapidly progressive disease that is not correlated with traditional risk factors such as smoking, alcohol consumption, or human papillomavirus (HPV) infection. The aim of the study was to identify genetic alterations associated with early-onset OSCC progression. The study included 25 young patients with OSCC living in the Russian Federation. Whole-exome sequencing of primary tumor and peripheral blood samples was performed using the SureSelect XT v. 8.0 DNA library preparation kit on the Genolab M platform. Analysis of single nucleotide variants (SNVs) and insertions and deletions (indels) was performed using the GATK pipeline; filtering of genetic variants in the tumor relative to those in the peripheral blood was performed using the Mutect2 pipeline; mutation annotation was performed using ANNOVAR. Statistical data processing was performed using the IBM SPSS Statistics 20 software package. To test mutations that showed a statistically significant result in relation to relapse-free, metastasis-free, and overall survival, data from the Cancer Genome Atlas (N = 127) were used. There was revealed the prognostic significance of somatic mutations in the TAF1L, CUL7, PRPS1L1, and CDKN2A genes for relapse-free survival (p = 0.003, p = 0.003, p = 0.003, and p = 0.004 respectively), PLEC and TEP1 for metastasis-free survival (p < 0.001 and p = 0.007 respectively), and ADGRL3, PREX1, and CDKN2A for overall survival (p = 0.023, p = 0.023, and p < 0.001 respectively). All mutations in the CDKN2A gene were frameshift or resulted in a premature termination codon; one patient was found to have a pathogenic variant rs121913387. For the CUL7 gene, the variant rs369167170 was recurrent in patients with relapses, and for the PLEC gene, the variant in the region 7:18027430 C>A was recurrent in patients with metastases. Analysis of the data from The Cancer Genome Atlas confirmed the association of only mutations of CDKN2A with OSCC progression at the age of 45 years (N = 18, p = 0.049), but not in older patients (N = 109). This work revealed genetic alterations associated with the progression of early-onset OSCC, which require confirmation of their significance in a larger sample of patients and an assessment of their functional significance.