Biases in mutation rate can influence molecular evolution, yielding rates of evolution that vary widely in different parts of the genome and even among neighboring nucleotides. Here, we explore one possible mechanism of influence on sequence-specific mutation rates, the electron-hole, which can localize and potentially trigger a replication mismatch. A hole is a mobile site of positive charge created during one-electron oxidation by, for example, radiation, contact with a mutagenic agent, or oxidative stress. Its quantum wavelike properties cause it to localize at various sites with probabilities that vary widely, by orders of magnitude, and depend strongly on the local sequence. We find significant correlations between hole probabilities and mutation rates within base triplets, observed in published mutation accumulation experiments on four species of bacteria. We have also computed hole probability spectra for hypervariable segment I of the human mtDNA control region, which contains several mutational hotspots, and for heptanucleotides in noncoding regions of the human genome, whose polymorphism levels have recently been reported. We observe significant correlations between hole probabilities, and context-specific mutation and substitution rates. The correlation with hole probability cannot be explained entirely by CpG methylation in the heptanucleotide data. Peaks in hole probability tend to coincide with mutational hotspots, even in mtDNA where CpG methylation is rare. Our results suggest that hole-enhanced mutational mechanisms, such as oxidation-stabilized tautomerization and base deamination, contribute to molecular evolution.
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http://dx.doi.org/10.1093/gbe/evy060 | DOI Listing |
Clin Lymphoma Myeloma Leuk
December 2024
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Hematology Center, Peking University People's Hospital, Qingdao, China. Electronic address:
Aim: To describe tyrosine kinase inhibitor (TKI) treatment patterns and analyze co-variates of TKI switch for chronic myeloid leukemia (CML) patients in a center from China.
Methods: A retrospectively study was designed to analyze TKI switching patterns, reasons and associated covariates in patients with CP-CML.
Results: 1766 patients receiving initial imatinib (n = 1374), nilotinib (n = 254), dasatinib (n = 63) and flumatinib (n = 75) therapy were retrospectively interrogated.
Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).
View Article and Find Full Text PDFTransl Cancer Res
December 2024
Department of Biomedical Engineering, School of Life Sciences, Guangxi Medical University, Nanning, China.
Background: The persistently high mortality and morbidity rates of hepatocellular carcinoma (HCC) remain a global concern. Notably, the disruptions in mitochondrial cholesterol metabolism (MCM) play a pivotal role in the progression and development of HCC, underscoring the significance of this metabolic pathway in the disease's etiology. The purpose of this research was to investigate genes associated with MCM and develop a model for predicting the prognostic features of patients with HCC.
View Article and Find Full Text PDFTransl Cancer Res
December 2024
Department of Radiation Oncology, The Second Hospital of Lanzhou University, Lanzhou, China.
Background: Within the realm of primary brain tumors, specifically glioblastoma (GBM), presents a notable obstacle due to their unfavorable prognosis and differing median survival rates contingent upon tumor grade and subtype. Despite a plethora of research connecting cardiotrophin-1 (CTF1) modifications to a range of illnesses, its correlation with glioma remains uncertain. This study investigated the clinical value of CTF1 in glioma and its potential as a biomarker of the disease.
View Article and Find Full Text PDFHeliyon
July 2024
Department of Breast Surgery, Institute of Breast Disease, Second Hospital of Dalian Medical University, Zhongshan Road, Dalian, 116023, Liaoning, China.
Identifying driver genes in cancer is a difficult task because of the heterogeneity of cancer as well as the complex interactions among genes. As sequencing data become more readily available, there is a growing need for detecting cancer driver genes based on statistical and mathematical modeling methods. Currently, plenty of driver gene identification algorithms have been published, but they fail to achieve consistent results.
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