Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma

Cancer. 2018 Jan 1;124(1):84-94. doi: 10.1002/cncr.31063. Epub 2017 Oct 20.

Abstract

Background: Human immunodeficiency virus-infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non-HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non-HIV-related HNSCC.

Methods: The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non-HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA-A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups.

Results: HIV-related HNSCC revealed a distinct pattern of mutations in comparison with non-HIV-related HNSCC. TP53 mutation frequencies were significantly lower in HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53.

Conclusions: HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2018;124:84-94. © 2017 American Cancer Society.

Keywords: TP53 gene; head and neck cancer; human immunodeficiency virus (HIV); human papillomavirus (HPV); mutation.

MeSH terms

  • Adult
  • Aged
  • Cadherins / genetics
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • Caspase 8 / genetics
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Cyclin D1 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics
  • ErbB Receptors / genetics
  • F-Box-WD Repeat-Containing Protein 7 / genetics
  • Female
  • HIV Infections / complications*
  • HLA-A Antigens / genetics
  • Head and Neck Neoplasms / complications
  • Head and Neck Neoplasms / genetics*
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Humans
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins / genetics
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • LIM Domain Proteins / genetics
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / genetics
  • Nuclear Proteins / genetics
  • Papillomaviridae / genetics
  • Papillomavirus Infections / complications
  • Protein Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Receptor, Notch1 / genetics
  • Receptor, Notch2 / genetics
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Squamous Cell Carcinoma of Head and Neck
  • Transcription Factors / genetics
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Proteins / genetics

Substances

  • AJUBA protein, human
  • CCND1 protein, human
  • CDKN2A protein, human
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • F-Box-WD Repeat-Containing Protein 7
  • FAT1 protein, human
  • FBXW7 protein, human
  • HLA-A Antigens
  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • LIM Domain Proteins
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • NOTCH1 protein, human
  • NOTCH2 protein, human
  • Nuclear Proteins
  • Receptor, Notch1
  • Receptor, Notch2
  • Receptors, Transforming Growth Factor beta
  • TP53 protein, human
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Cyclin D1
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • NSD1 protein, human
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • CASP8 protein, human
  • Caspase 8
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)