Genomic landscape of virus-associated cancers
Abstract It has been estimated that 15%-20% of human cancers are attributable to infections, mostly by carcinogenic viruses. The incidence varies worldwide, with a majority affecting developing countries. Here, we conduct a comparative analysis of virus-positive and virus-negative tumors in nine can...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60836-9 |
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| author | Yoonhee Nam Karen Gomez Jean-Baptiste Reynier Cole Khamnei Michael Aitken Vivian Zheng Tenzin Lhakhang Milena Casula Giuseppe Palmieri Antonio Cossu Arnold Levine Enrico Tiacci Raul Rabadan |
| author_facet | Yoonhee Nam Karen Gomez Jean-Baptiste Reynier Cole Khamnei Michael Aitken Vivian Zheng Tenzin Lhakhang Milena Casula Giuseppe Palmieri Antonio Cossu Arnold Levine Enrico Tiacci Raul Rabadan |
| author_sort | Yoonhee Nam |
| collection | DOAJ |
| description | Abstract It has been estimated that 15%-20% of human cancers are attributable to infections, mostly by carcinogenic viruses. The incidence varies worldwide, with a majority affecting developing countries. Here, we conduct a comparative analysis of virus-positive and virus-negative tumors in nine cancers linked to five viruses. We observe a higher frequency of virus-positive tumors in males, with notable geographic differences in incidence. Our genomic analysis of 1971 tumors reveals a lower somatic burden, distinct mutation signatures, and driver gene mutations in virus-positive tumors. Compared to virus-negative cases, virus-positive cases have fewer mutations of TP53, CDKN2A, and deletions of 9p21.3/CDKN2A-CDKN1A while exhibiting more mutations in RNA helicases DDX3X and EIF4A1. Furthermore, an analysis of clinical trials of PD-(L)1 inhibitors suggests an association of virus-positivity with higher treatment response rate, particularly evident in gastric cancer and head and neck squamous cell carcinoma. Both cancer types also show evidence of increased CD8 + T cell infiltration and T cell receptor clonal selection in virus-positive tumors. These results illustrate the epidemiological, genetic, and therapeutic trends across virus-associated malignancies. |
| format | Article |
| id | doaj-art-64d6b8ded3f34c5daa744c207ab4b764 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-64d6b8ded3f34c5daa744c207ab4b7642025-08-20T03:45:31ZengNature PortfolioNature Communications2041-17232025-07-0116111610.1038/s41467-025-60836-9Genomic landscape of virus-associated cancersYoonhee Nam0Karen Gomez1Jean-Baptiste Reynier2Cole Khamnei3Michael Aitken4Vivian Zheng5Tenzin Lhakhang6Milena Casula7Giuseppe Palmieri8Antonio Cossu9Arnold Levine10Enrico Tiacci11Raul Rabadan12Program for Mathematical Genomics and Department of Systems Biology, Columbia UniversityProgram for Mathematical Genomics and Department of Systems Biology, Columbia UniversityProgram for Mathematical Genomics and Department of Systems Biology, Columbia UniversityProgram for Mathematical Genomics and Department of Systems Biology, Columbia UniversityProgram for Mathematical Genomics and Department of Systems Biology, Columbia UniversityProgram for Mathematical Genomics and Department of Systems Biology, Columbia UniversityProgram for Mathematical Genomics and Department of Systems Biology, Columbia UniversityUnit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR)Unit of Cancer Genetics, Institute of Genetic Biomedical Research (IRGB), National Research Council (CNR)Department of Medicine, Surgery and Pharmacy, University of SassariSimons Center for Systems Biology, Institute for Advanced StudyInstitute of Hematology and Center for Hemato-Oncology Research, Department of Medicine and Surgery, University and Hospital of PerugiaProgram for Mathematical Genomics and Department of Systems Biology, Columbia UniversityAbstract It has been estimated that 15%-20% of human cancers are attributable to infections, mostly by carcinogenic viruses. The incidence varies worldwide, with a majority affecting developing countries. Here, we conduct a comparative analysis of virus-positive and virus-negative tumors in nine cancers linked to five viruses. We observe a higher frequency of virus-positive tumors in males, with notable geographic differences in incidence. Our genomic analysis of 1971 tumors reveals a lower somatic burden, distinct mutation signatures, and driver gene mutations in virus-positive tumors. Compared to virus-negative cases, virus-positive cases have fewer mutations of TP53, CDKN2A, and deletions of 9p21.3/CDKN2A-CDKN1A while exhibiting more mutations in RNA helicases DDX3X and EIF4A1. Furthermore, an analysis of clinical trials of PD-(L)1 inhibitors suggests an association of virus-positivity with higher treatment response rate, particularly evident in gastric cancer and head and neck squamous cell carcinoma. Both cancer types also show evidence of increased CD8 + T cell infiltration and T cell receptor clonal selection in virus-positive tumors. These results illustrate the epidemiological, genetic, and therapeutic trends across virus-associated malignancies.https://doi.org/10.1038/s41467-025-60836-9 |
| spellingShingle | Yoonhee Nam Karen Gomez Jean-Baptiste Reynier Cole Khamnei Michael Aitken Vivian Zheng Tenzin Lhakhang Milena Casula Giuseppe Palmieri Antonio Cossu Arnold Levine Enrico Tiacci Raul Rabadan Genomic landscape of virus-associated cancers Nature Communications |
| title | Genomic landscape of virus-associated cancers |
| title_full | Genomic landscape of virus-associated cancers |
| title_fullStr | Genomic landscape of virus-associated cancers |
| title_full_unstemmed | Genomic landscape of virus-associated cancers |
| title_short | Genomic landscape of virus-associated cancers |
| title_sort | genomic landscape of virus associated cancers |
| url | https://doi.org/10.1038/s41467-025-60836-9 |
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