HPV Meets APOBEC: New Players in Head and Neck Cancer

Riva, Giuseppe; Albano, Camilla; Gugliesi, Francesca; Pasquero, Selina; Pacheco, Sergio Fernando Castillo; Pecorari, Giancarlo; Landolfo, Santo; Biolatti, Matteo; Dell’Oste, Valentina

doi:10.3390/ijms22031402

Cited by 28 publications

(23 citation statements)

References 102 publications

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“…The APOBEC family has been shown to induce tumor mutations by aberrant DNA editing mechanisms ( 49 ). Infection with high-risk HPV, which is one of the pathogenic factors in the oral and maxillofacial regions, leads to increased APOBEC family activity ( 50 – 52 ).…”

Section: Discussionmentioning

confidence: 99%

Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing

Gong

Zheng

et al. 2022

Front. Oncol.

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Multiple primary cancers (MPCs) refer to cancers that occur simultaneously or metachronously in the same individual. The incidence of MPC has increased recently, as the survival time of malignant tumor patients has been greatly prolonged. It is difficult to differentiate MPC from primary cancers (PCs) in the same anatomical region from the clinical manifestation alone. However, their biological behaviors appear to be distinct. In this study, we show that the prognosis of multiple primary oral cancers (MP-OCs) is worse than primary oral cancers (P-OCs). To better understand the molecular mechanisms of MP-OC, we used whole exome sequencing (WES) to analyze samples from 9 patients with MP-OC and 21 patients with P-OC. We found more somatic mutations in MP-OC than in P-OC. MP-OC had more complicated mutation signatures, which were associated with age-related and Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) activity-related signatures. Tumor mutational burden (TMB) and mutant-allele tumor heterogeneity (MATH) of MP-OC trended higher compared to P-OC. KEGG and GO analysis showed the differential pathways of MP-OC versus P-OC. In addition, MP-OC took amplification, not loss, as the main pattern of copy number variation (CNV), while P-OC took both. Lastly, we did not find significantly different mutant germline genes, but MSH-6 mutation may be a potential MP-OC driver. In short, our preliminary results show that MP-OC and P-OC have different molecular characteristics.

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Section: Discussionmentioning

confidence: 99%

Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing

Gong

Zheng

et al. 2022

Front. Oncol.

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“…HNSCC is usually associated with exposure to tobacco-derived carcinogens, excessive alcohol consumption, or both. Tumors appearing in the oropharynx are increasingly related to human papillomavirus (HPV) carcinogenic strains, mainly HPV-16, and to a lesser extent HPV-18 and other strains of infection ( Riva et al, 2021 ). In current treatment methods, only about 50% of HNSCC patients survive for more than 5 years.…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

Wang

Yang

Ming

et al. 2021

Front. Cell Dev. Biol.

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Background: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether m6A/m5C/m1A-related long non-coding RNAs (lncRNAs) affect the prognosis of head and neck squamous cell carcinoma (HNSCC).Methods: We summarized 52 m6A/m5C/m1A-related genes, downloaded 44 normal samples and 501 HNSCC tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database, and then searched for m6A/m5C/m1A-related genes co-expressed lncRNAs. We adopt the least absolute shrinkage and selection operator (LASSO) Cox regression to obtain m6A/m5C/m1A-related lncRNAs to construct a prognostic signature of HNSCC.Results: This prognostic signature is based on six m6A/m5C/m1A-related lncRNAs (AL035587.1, AC009121.3, AF131215.5, FMR1-IT1, AC106820.5, PTOV1-AS2). It was found that the high-risk subgroup has worse overall survival (OS) than the low-risk subgroup. Moreover, the results showed that most immune checkpoint genes were significantly different between the two risk groups (p < 0.05). Immunity microenvironment analysis showed that the contents of NK cell resting, macrophages M2, and neutrophils in samples of low-risk group were significantly lower than those of high-risk group (p < 0.05), while the contents of B cells navie, plasma cells, and T cells regulatory (Tregs) were on the contrary (p < 0.05). In addition, patients with high tumor mutational burden (TMB) had the worse overall survival than those with low tumor mutational burden.Conclusion: Our study elucidated how m6A/m5C/m1A-related lncRNAs are related to the prognosis, immune microenvironment, and TMB of HNSCC. In the future, these m6A/m5C/m1A-related lncRNAs may become a new choice for immunotherapy of HNSCC.

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“…Deficiency of homologous recombination [ 75 ] and replication stress [ 80 ] have been linked to HPV integration and pathogenicity. Work from our group and others have demonstrated that APOBEC plays a key role in HPV-mediated carcinogenesis in the oropharynx [ 81 ], and increased expression and activity of APOBEC3B and APOBEC3A, respectively, have been linked to direct actions of HPV oncoproteins E6 and E7 [ 82 ]. APOBEC3s have been associated with genomic instability across multiple cancer types [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration

Schrank

Kim

Rehmani

et al. 2022

Cancers

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Squamous cell carcinoma of the oropharynx caused by HPV type 16 (HPV16+ OPSCC) is the most common HPV-associated malignancy in the USA and has many molecular differences from uterine cervical squamous cell carcinoma (UCSCC). Our understanding of HPV oncogenesis relied on studies of UCSCC revealing a consensus model reliant on HPV integration with a loss of E2. Here, we compare patterns of HPV integration in UCSCC and OPSCC by analysis of affinity capture sequencing of the HPV16 genome in 104 OPSCC and 44 UCSCC tumors. These cohorts were contemporaneously sequenced using an identical strategy. Integration was identified using discordant read pair clustering and assembly-based approaches. Viral integration sites, structural variants, and copy losses were examined. While large-scale deep losses of HPV16 genes were common in UCSCC and were associated with E2 loss, deep copy losses of the HPV16 genome were infrequent in HPV16+ OPSCC. Similarly, structural variants within HPV16 favored E2 loss in UCSCC but not OPSCC. HPV16 integration sites were non-random, with recurrent integration hot-spots identified. OPSCC tumors had many more integration sites per tumor when compared to UCSCC and had more integration sites in genomic regions with high gene density. These data show that viral integration and E2 disruption are distinct in UCSCC and OPSCC. Our findings also add to growing literature suggesting that HPV tumorigenesis in OPSCC does not follow the model developed based on UCSCC.

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HPV Meets APOBEC: New Players in Head and Neck Cancer

Cited by 28 publications

References 102 publications

Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing

Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing

The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration

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