学術雑誌論文

学術雑誌論文

Nature Communications. 2025, 16(1), p. 1052

Intratumor heterogeneity of HPV integration in HPV-associated head and neck cancer

Nature Research

英語

2025-01-26

https://doi.org/10.1038/s41467-025-56150-z

Sasa N., Kishikawa T., Mori M., et al. Intratumor heterogeneity of HPV integration in HPV-associated head and neck cancer. Nature Communications 16, 1052 (2025); https://doi.org/10.1038/s41467-025-56150-z.

Integration of human papillomavirus (HPV) into the host genome drives HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC). Whole-genome sequencing of 51 tumors revealed intratumor heterogeneity of HPV integration, with 44% of breakpoints subclonal, and a biased distribution of integration breakpoints across the HPV genome. Four HPV physical states were identified, with at least 49% of tumors progressing without integration. HPV integration was associated with APOBEC-induced broad genomic instability and focal genomic instability, including structural variants at integration sites. HPV+ HNSCCs exhibited almost no smoking-induced mutational signatures. Heterozygous loss of ataxia-telangiectasia mutated (ATM) was observed in 67% of tumors, with its downregulation confirmed by single-cell RNA sequencing and immunohistochemistry, suggesting ATM haploinsufficiency contributes to carcinogenesis. PI3K activation was the major oncogenic mutation, with JAK-STAT activation in tumors with clonal integration and NF-kappa B activation in those without. These findings provide valuable insights into HPV integration in HPV+ HNSCC.

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

101047

Intratumor heterogeneity of HPV integration in HPV-associated head and neck cancer

Nature Research

英語

2025-01-26

Nature Communications

16

1

1052

https://doi.org/10.1038/s41467-025-56150-z

https://hdl.handle.net/11094/101047