Somatic mutations in 3929 HPV positive cervical cells associated with infection outcome and HPV type.

Autor: Pinheiro M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA., Wentzensen N; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA., Dean M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD, USA., Yeager M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD, USA.; Department of Biology, Hood College, Frederick, MD, USA., Chen Z; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China., Shastry A; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD, USA., Boland JF; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD, USA., Bass S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD, USA., Burdett L; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD, USA., Lorey T; Regional Laboratory and Women's Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA., Mishra S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick, MD, USA., Castle PE; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD, USA., Schiffman M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA., Burk RD; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.; Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA., Zhu B; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA., Mirabello L; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. mirabellol@mail.nih.gov.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 12; Vol. 15 (1), pp. 7895. Date of Electronic Publication: 2024 Sep 12.
DOI: 10.1038/s41467-024-51713-y
Abstrakt: Invasive cervical cancers (ICC), caused by HPV infections, have a heterogeneous molecular landscape. We investigate the detection, timing, and HPV type specificity of somatic mutations in 3929 HPV-positive exfoliated cervical cell samples from individuals undergoing cervical screening in the U.S. using deep targeted sequencing in ICC cases, precancers, and HPV-positive controls. We discover a subset of hotspot mutations rare in controls (2.6%) but significantly more prevalent in precancers, particularly glandular precancer lesions (10.2%), and cancers (25.7%), supporting their involvement in ICC carcinogenesis. Hotspot mutations differ by HPV type, and HPV18/45-positive ICC are more likely to have multiple hotspot mutations compared to HPV16-positive ICC. The proportion of cells containing hotspot mutations is higher (i.e., higher variant allele fraction) in ICC and mutations are detectable up to 6 years prior to cancer diagnosis. Our findings demonstrate the feasibility of using exfoliated cervical cells for detection of somatic mutations as potential diagnostic biomarkers.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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