Distinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma
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John Wiley and Sons Inc.
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. © 2017 American Cancer Society
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Keywords
Head and neck cancer, Human immunodeficiency virus (hiv), Human papillomavirus (hpv), Mutation, Tp53 gene, Adult, Aged, Cadherins, Carcinoma, squamous cell, Case-control studies, Caspase 8, Class i phosphatidylinositol 3-kinases, Cyclin d1, Cyclin-dependent kinase inhibitor p18, F-box-wd repeat-containing protein 7, Female, Head and neck neoplasms, Hiv infections, Hla-a antigens, Humans, In situ hybridization, Intracellular signaling peptides and proteins, Kelch-like ech-associated protein 1, Lim domain proteins, Male, Middle aged, Nf-e2-related factor 2, Nuclear proteins, Papillomaviridae, Papillomavirus infections, Protein-serine-threonine kinases, Proto-oncogene proteins p21(ras), Receptor, epidermal growth factor, Receptor, notch1, Receptor, notch2, Receptors, transforming growth factor beta, Transcription factors, Tumor suppressor protein p53, Tumor suppressor proteins, Cyclin dependent kinase inhibitor 2a, Dna, Epidermal growth factor receptor, Hla a antigen, Kelch like ech associated protein 1, Notch1 receptor, Notch2 receptor, Protein p16, Protein p53, Ajuba protein, human, Cadherin, Casp8 protein, human, Ccnd1 protein, human, Cdkn2a protein, human, Cyclin dependent kinase inhibitor 2c, Egfr protein, human, F box/wd repeat containing protein 7, Fat1 protein, human, Fbxw7 protein, human, Hras protein, human, Keap1 protein, human, Lim protein, Nfe2l2 protein, human, Notch1 protein, human, Notch2 protein, human, Nsd1 protein, human, Nuclear protein, Phosphatidylinositol 4,5 bisphosphate 3 kinase, Pik3ca protein, human, Protein p21, Protein serine threonine kinase, Signal peptide, Tp53 protein, human, Tp63 protein, human, Transcription factor, Transcription factor nrf2, Transforming growth factor beta receptor, Transforming growth factor-beta type ii receptor, Tumor suppressor protein, Ajuba gene, Article, Casp8 gene, Ccnd1 gene, Cdkn2a gene, Clinical article, Controlled study, Disease association, Dna library, Dna sequence, Egfr gene, Exon, Fat1 gene, Fbxw7 gene, Gene, Gene mutation, Head and neck squamous cell carcinoma, Hla a gene, Hras gene, Human, Human immunodeficiency virus, Immunohistochemistry, Keap1 gene, Multiplex polymerase chain reaction, Nfe2l2 gene, Nonhuman, Notch1 gene, Notch2 gene, Nsd1 gene, Nucleic acid base substitution, Pik3ca gene, Priority journal, Sequence analysis, Software, Tgfbr2 gene, Tp63 gene, Wart virus, Case control study, Complication, Genetics, Head and neck tumor, Human immunodeficiency virus infection, Papillomavirus infection, Squamous cell carcinoma