Gynecologic Oncology, Journal Year: 2024, Volume and Issue: 192, P. 65 - 72
Published: Nov. 14, 2024
Genomic instability has been proposed as a predictive biomarker for immunotherapy in ovarian cancer. We tested method measuring DNA damage, direct measure of genomic instability, tumors and its ability to predict response Vigil (gemogenovatucel-T).
Language: Английский
Nature, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 15, 2025
Abstract DNA is subject to continual damage, leaving each cell with thousands of individual lesions at any given moment 1–3 . The efficiency repair means that most known classes lesion have a half-life minutes hours 3,4 , but the extent which damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising 818 persisted across multiple cycles in normal human stem cells blood, liver and bronchial epithelium 5–12 Persistent occurred increased rates, distinctive mutational signatures, donors exposed tobacco or chemotherapy, suggesting they arise exogenous mutagens. In haematopoietic cells, persistent lesions, probably endogenous sources, generated characteristic signature SBS19 13 ; steadily throughout life, including utero; endured 2.2 years on average, 15–25% lasting least 3 years. We estimate has approximately eight such time, half will generate mutation cycle. Overall, 16% blood are attributable SBS19, similar proportions driver cancers exhibit this signature. These data indicate existence family mutagens, present low numbers per genome, months years, substantial fraction burden somatic cells.
Language: Английский
Citations
4
Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown
Published: Nov. 23, 2023
Abstract DNA suffers continual damage leaving a cell with thousands of individual lesions at any given moment 1–3 . The efficiency repair means that most known classes lesion have half-life minutes to hours 3,4 , but whether some can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising 832 persisted across multiple cycles in normal human stem cells blood, liver and bronchial epithelium 5–12 Persistent occurred increased rates, distinctive mutational signatures, donors exposed tobacco or chemotherapy, suggesting they arise exogenous mutagens. In haematopoietic cells, persistent lesions, likely endogenous sources, generated characteristic signature, so-called SBS19 13 ; steadily throughout life, including utero endured 1.5 years on average, 15% lasting 3+ years. We estimate has, ~4-5 such time, half which will generate mutation each cycle. Overall, 16% blood are attributable SBS19, similar proportions driver cancers exhibit this signature. These data imply the existence family both mutagens, present low numbers per genome persisting months years, sizable fractions cells’ burdens.
Language: Английский
Citations
4
Genes and Environment, Journal Year: 2024, Volume and Issue: 46(1)
Published: Feb. 8, 2024
Abstract The prevalence of cancer is increasing globally, and Malaysia no exception. exposome represents a paradigm shift in research, emphasizing the importance holistic approach that considers cumulative effect diverse exposures encountered throughout life. include dietary factors, air water pollutants, occupational hazards, lifestyle choices, infectious agents social determinants health. concept acknowledges each individual’s risk shaped by not only their genetic makeup but also unique life experiences environmental interactions. This comprehensive review was conducted systematically searching scientific databases such as PubMed, Scopus Google Scholar, using keywords “exposomes (environmental AND/OR physical chemical exposures) AND Malaysia”, for relevant articles published between 2010 2023. Articles addressing relationship exposomes Malaysian population were critically evaluated summarized. aims to provide an update on epidemiological evidence linking with Malaysia. will current findings research related identified exposomes-omics interaction gap area subject matter. Understanding interplay complex carcinogenesis holds potential unveil novel preventive strategies may be beneficial public
Language: Английский
Citations
1
Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1173 - 1173
Published: Sept. 19, 2024
DNA adductomics is the global study of all adducts and was first proposed in 2006 by Matsuda group. Its development has been greatly credited to advances mass spectrometric techniques, particularly tandem multiple-stage spectrometry. In fact, liquid chromatography-mass spectrometry (LC-MS)-based methods are virtually sole technique with practicality for adductomic studies date. At present, primarily used as a tool search adducts, known unknown, providing evidence exposure exogenous genotoxins and/or molecular mechanisms their genotoxicity. Some discovered this way have potential predict cancer risks be associated adverse health outcomes. successfully identify determine carcinogens that may contribute etiology certain cancers, including bacterial an N-nitrosamine. Also using approach, multiple observed show age dependence serve aging biomarkers. These achievements highlight capability power medicine, biological science, environmental science. Nonetheless, still its infancy, great expected future.
Language: Английский
Citations
1
TrAC Trends in Analytical Chemistry, Journal Year: 2024, Volume and Issue: 180, P. 117900 - 117900
Published: Aug. 5, 2024
Language: Английский
Citations
0
Cancer Letters, Journal Year: 2024, Volume and Issue: 604, P. 217222 - 217222
Published: Sept. 7, 2024
Language: Английский
Citations
0
Gynecologic Oncology, Journal Year: 2024, Volume and Issue: 192, P. 65 - 72
Published: Nov. 14, 2024
Genomic instability has been proposed as a predictive biomarker for immunotherapy in ovarian cancer. We tested method measuring DNA damage, direct measure of genomic instability, tumors and its ability to predict response Vigil (gemogenovatucel-T).
Language: Английский
Citations
0