Nuclear factor I X is a recurrent target for HPV16 insertions in anal carcinomas

Jeannot, Emmanuelle; Harlé, Alexandre; Holmes, Allyson; Sastre-Garau, Xavier

doi:10.1002/gcc.22675

Cited by 12 publications

(11 citation statements)

References 57 publications

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“…These recurrent insertions were not detected in HPV-positive ASCC. In contrast, integration into the NFIX gene was observed in four cases, confirming the results from the recent study by Jeannot et al [15], along with three other integration events adjacent to the NFIX gene but nonintragenic, of unknown significance. NFIX belongs to the NFI gene family, consisting of four transcription factors (NFIA, NFIB, NFIC, and NFIX), involved in the regulation of cell proliferation and differentiation.…”

Section: Discussionsupporting

confidence: 89%

“…The distribution of the various HPV integration signatures differed between ASCC and cervical cancers and was associated with viral load and PIK3CA mutation [18]. The small number of events in this single-center study may have limited the statistical power to determine whether HPV status and integration signatures have a prognostic or predictive impact in HPV-positive ASCC, but was nevertheless sufficient to confirm recurrent targeting of NFIX by HPV insertion in ASCC, a potential favorable prognostic factor [15]. Further studies on larger, multicenter cohorts of anal and other HPV-associated tumors are warranted.…”

Section: Discussionmentioning

confidence: 86%

“…HPV is a small double-strand DNA virus, of approximately 8000 base pairs, with more than 150 different genotypes. The viral genome is either maintained as extrachromosomal multicopy nuclear episomes or integrated into the host genome [14,15]. Viral oncogenesis involves the expression of E6 and E7 proteins, which are able to interact with and inhibit p53 and pRb tumor suppressor proteins [16].…”

Section: Introductionmentioning

confidence: 99%

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Mechanistic Signatures of Human Papillomavirus Insertions in Anal Squamous Cell Carcinomas

Morel

Neuzillet

Wack

et al. 2019

Cancers

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The role of human papillomavirus (HPV) in anal squamous cell carcinoma (ASCC) carcinogenesis has been clearly established, involving the expression of viral oncoproteins and optional viral DNA integration into the host genome. In this article, we describe the various mechanisms and sites of HPV DNA insertion and assess their prognostic and predictive value in a large series of patients with HPV-positive ASCC with long-term follow-up. We retrospectively analyzed 96 tumor samples from 93 HPV-positive ASCC patients using the Capture-HPV method followed by Next-Generation Sequencing, allowing determination of HPV genotype and identification of the mechanisms and sites of viral genome integration. We identified five different mechanistic signatures of HPV insertions. The distribution of HPV signatures differed from that previously described in HPV-positive cervical carcinoma (p < 0.001). In ASCC samples, the HPV genome more frequently remained in episomal form (45.2%). The most common signature of HPV insertion was MJ-SC (26.9%), i.e., HPV–chromosomal junctions scattered at different loci. Functionally, HPV integration signatures were not associated with survival or response to treatment, but were associated with viral load (p = 0.022) and PIK3CA mutation (p = 0.0069). High viral load was associated with longer survival in both univariate (p = 0.044) and multivariate (p = 0.011) analyses. Finally, HPV integration occurred on most human chromosomes, but intragenic integration into the NFIX gene was recurrently observed (n = 4/51 tumors). Overall, the distribution of mechanistic signatures of HPV insertions in ASCC was different from that observed in cervical carcinoma and was associated with viral load and PIK3CA mutation. We confirmed recurrent targeting of NFIX by HPV integration, suggesting a role for this gene in ASCC carcinogenesis.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Mechanistic Signatures of Human Papillomavirus Insertions in Anal Squamous Cell Carcinomas

Morel

Neuzillet

Wack

et al. 2019

Cancers

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“…The HBV regions included in this integrant are shown in Figure 2 D. The insertion point of human chromosome 17 is the coiled-coil domain-containing 57 (CCDC57) coding region. It has been reported that CCDC57 is one of the genes targeted by the integration of human papillomavirus 16 (HPV 16) [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

Analysis of HBV Genomes Integrated into the Genomes of Human Hepatoma PLC/PRF/5 Cells by HBV Sequence Capture-Based Next-Generation Sequencing

Ishii

Tamura

Shibata

et al. 2020

Genes

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Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC) worldwide. The integration of HBV genomic DNA into the host genome occurs randomly, early after infection, and is associated with hepatocarcinogenesis in HBV-infected patients. Therefore, it is important to analyze HBV genome integration. We analyzed HBV genome integration in human hepatoma PLC/PRF/5 cells by HBV sequence capture-based next-generation sequencing (NGS) methods. We confirmed the results by using Sanger sequencing methods. We observed that HBV genotype A is integrated into the genome of PLC/PRF/5 cells. HBV sequence capture-based NGS is useful for the analysis of HBV genome integrants and their locations in the human genome. Among the HBV genome integrants, we performed functional analysis and demonstrated the automatic expression of some HBV proteins encoded by HBV integrants from chromosomes 3 and 11 in Huh7 cells transfected with these DNA sequences. HBV sequence capture-based NGS may be a useful tool for the assessment of HBV genome integration into the human genome in clinical samples and suggests new strategies for hepatocarcinogenesis in HBV infection.

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“…FLOT1 also induces EMT and alters cell cycle by modulating Erk/Akt signaling axis 31 . Besides, the prognostic value of IL20RB was actively discussed in multiple tumors including glaucoma, anal cancer and lung adenocarcinoma [32][33][34] . Moreover, MAPKAPK3 is a member of stress-responsive kinase that induces autophagy in terms of stress (in ammation, infection and starvation)and thus determining cell fate 35,36 .…”

Section: Discussionmentioning

confidence: 99%

Identification of an immune-related gene signature to improve prognosis prediction of colorectal cancer patients

Dai

Yao

et al. 2020

Preprint

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Background: Despite recent advance in immune therapy, great heterogeneity exists in colorectal cancer (CRC) patients’ outcome. In this study, we aimed to analyze the Immune-related gene (IRG) expression profiles from two independent public databases and develop an effective signature to forecast patients’ prognosis.Method: IRGs were collected from The Cancer Genome Atlas (TCGA) database to identify a prognostic genes signature, which was verified in Gene Expression Omnibus (GEO) database. Gene function enrichment and immune cell infiltration analyses were conducted. A prognostic nomogram was built incorporating the IRG signature with clinical risk factors.Results: The training and test datasets had 487 and 579 patients, respectively. A prognostic six-gene-signature (CCL22, LIMK1, MAPKAPK3, FLOT1, GPRC5B and IL20RB) was developed through feature selection, and yielded incredible differentiation between low and high-risk group in the training set (P < 0.001), which was confirmed in the test group (P < 0.001). The signature outperformed tumor staging regarding survival prediction. Go and KEGG functional annotation analysis suggested the signature were significantly enriched in metabolic process and regulation of immunity (P<0.05). When combined with clinical risk factors, the model showed robust prediction capability.Conclusion: The immune-related six-gene signature is a reliable prognostic indicator for CRC patients and could bring insight for personalized cancer management.

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Nuclear factor I X is a recurrent target for HPV16 insertions in anal carcinomas

Cited by 12 publications

References 57 publications

Mechanistic Signatures of Human Papillomavirus Insertions in Anal Squamous Cell Carcinomas

Mechanistic Signatures of Human Papillomavirus Insertions in Anal Squamous Cell Carcinomas

Analysis of HBV Genomes Integrated into the Genomes of Human Hepatoma PLC/PRF/5 Cells by HBV Sequence Capture-Based Next-Generation Sequencing

Identification of an immune-related gene signature to improve prognosis prediction of colorectal cancer patients

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