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

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.

Exploring the Mechanism of Flavonoids Through Systematic Bioinformatics Analysis

“…Specifically, isoflavones are a type of naturally occurring isoflavonoids, which act as phytoestrogens in mammals, their targets were mainly distributed in module 1, 2, and 5 ( Supplementary Figure 6 ). Previous researches indicated that BRCA1 in module 1 was associated with risk of estrogen-receptor-negative breast cancer ( Milne et al, 2017 ), NFE2L2 in module 3 was related with cell multisystem disorder ( Huppke et al, 2017 ), and TP53 in module 5 was related with human immunodeficiency virus-related head and neck squamous cell carcinoma ( Gleber-Netto et al, 2018 ).…”

Telomerase promoter mutations in human immunodeficiency virus-related conjunctiva neoplasia

“…A recent report compared the pattern of mutations among HIV-related and non-HIV related head and neck SCC in genes known to be frequently mutated in such tumours and identified a different pattern of nucleotide changes in all mutated genes including TP53 [ 22 ]. Particularly, they observed an enrichment of C>T changes in the HIV-infected cases likely caused by the cytosine deamination [ 34 ].…”

“…Very few studies have compared the mutation profile of tumours arising in HIV-positive patients versus those without HIV infection. Gleber-Netto et al [ 22 ] analyzed the nucleotide sequence of 18 genes in HIV-related and non-HIV-related head and neck SCC and showed that among HIV-positive patients the mutations tended to be TpC>T in all mutated genes but especially in TP53. This type of nucleotide change is mainly caused by the activity of APOBEC family cytosine deaminases as host defence against viral infections which also cause nucleotide mutations in human DNA [ 23 , 24 ].…”

Telomeric Repeat-Containing RNAs (TERRA) Decrease in Squamous Cell Carcinoma of the Head and Neck Is Associated with Worsened Clinical Outcome

“…In addition, it was shown that human papilloma virus (HPV) is involved in the pathogenesis of a subgroup of HNSCCs. HPV is a risk factor for cancer of the oropharynx, particularly in tumors that are not associated with p53 mutations or with other risk factor such as tobacco and alcohol [ 22 , 23 ]. Based on this evidence it has been suggested that oropharyngeal cancer develops through two different pathways: the first one related to tobacco/alcohol consumption and p53 mutation, and the second one to HPV infection and genome instability.…”