One challenge for multicellular organisms is maintaining genome stability in the face of mutagens across long life spans. Imperfect genome maintenance leads to mutation accumulation in somatic cells, which is associated with tumors and senescence in vertebrates. Colonial reef-building corals are often large, can live for hundreds of years, rarely develop recognizable tumors, and are thought to convert somatic cells into gamete producers, so they are a pivotal group in which to understand long-term genome maintenance. To measure rates and patterns of somatic mutations, we analyzed transcriptomes from 17 to 22 branches from each of four Acropora hyacinthus colonies, determined putative single nucleotide variants, and verified them with Sanger resequencing. Unlike for human skin carcinomas, there is no signature of mutations caused by UV damage, indicating either higher efficiency of repair than in vertebrates, or strong sunscreen protection in these shallow water tropical animals. The somatic mutation frequency per nucleotide in A. hyacinthus is on the same order of magnitude (10-7) as noncancerous human somatic cells, and accumulation of mutations with age is similar. Loss of heterozygosity variants outnumber gain of heterozygosity mutations ∼2:1. Although the mutation frequency is similar in mammals and corals, the preponderance of loss of heterozygosity changes and potential selection may reduce the frequency of deleterious mutations in colonial animals like corals. This may limit the deleterious effects of somatic mutations on the coral organism as well as potential offspring.
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http://dx.doi.org/10.1093/molbev/msz270 | DOI Listing |
Front Immunol
January 2025
Centro de Investigaciones Oncológicas (FUCA), Fundación Cáncer, Ciudad Autónoma de Buenos Aires, Argentina.
VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient's private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL's somatic mutations and human polymorphisms remain unexplored.
View Article and Find Full Text PDFPrecis Clin Med
March 2025
Department of Gynecology and Obstetrics, CIO ABCD, University Hospital Düsseldorf, Düsseldorf 40225, Germany.
Background: Circulating cell-free tumor DNA (ctDNA) provides a non-invasive approach for assessing somatic alterations. The German PRAEGNANT registry study aims to explore molecular biomarkers and investigate their integration into clinical practice. In this context, ctDNA testing was included to understand the motivations of clinicians to initiate testing, to identify somatic alterations, and to assess the clinical impact of the results obtained.
View Article and Find Full Text PDFAims: The prognostic impact of B lymphocytes surrounding Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) and pathogenic variants in genes associated with apoptosis regulation remains undefined.
Methods: We have quantified the proportion of B lymphocytes in tumour microenvironment (TME) in 220 diagnostic slides from 110 cHL patients applying computational pathology (CP) and sequenced cases using a targeted panel including 47 genes recurrently mutated in mature B-cell neoplasms. Kaplan-Meier estimators and multivariate Cox regression on overall survival (OS) and progression-free survival (PFS) were assessed following the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines.
Primary apocrine adenocarcinoma, a rare malignancy, is an aggressive tumor rarely reported. It has diagnostic and treatment challenges as it is difficult to distinguish it from metastases due to breast carcinoma. Currently, no data are available for the use of next-generation sequencing to identify the possibility of targeted therapies for metastatic disease.
View Article and Find Full Text PDFBioData Min
January 2025
Biotechnology Research and Innovation Council-National Institute of Biomedical Genomics (BRIC-NIBMG), National Institute of Biomedical Genomics, Kalyani, West Bengal, India.
Background And Objective: Accurate identification and prioritization of driver-mutations in cancer is critical for effective patient management. Despite the presence of numerous bioinformatic algorithms for estimating mutation pathogenicity, there is significant variation in their assessments. This inconsistency is evident even for well-established cancer driver mutations.
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