Carcinogen susceptibility is regulated by genome architecture and predicts cancer mutagenesis

In this study, we present the first quantitative human genome-wide map of DNA lesions induced by ultraviolet (UV) radiation, the ubiquitous carcinogen in sunlight that causes skin cancer. Remarkably, the pattern of carcinogen susceptibility across the genome of primary cells significantly reflects mutation frequency in malignant melanoma. Surprisingly, DNase-accessible euchromatin is protected from UV, while lamina-associated heterochromatin at the nuclear periphery is vulnerable. Many cancer driver genes have an intrinsic increase in carcinogen susceptibility, including the BRAF oncogene that has the highest mutation frequency in melanoma. These findings provide a genome-wide snapshot of DNA injuries at the earliest stage of carcinogenesis. Furthermore, they identify carcinogen susceptibility as an origin of genome instability that is regulated by nuclear architecture and mirrors mutagenesis in cancer.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Cancer, Chromatin, Epigenetics, Genomics & Functional Genomics, DNA Replication, Repair & Recombination Articles Source Type: research

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Patients Selection for Immunotherapy in Solid Tumors: Overcome the Naïve Vision of a Single Biomarker. Biomed Res Int. 2019;2019:9056417 Authors: Signorelli D, Giannatempo P, Grazia G, Aiello MM, Bertolini F, Mirabile A, Buti S, Vasile E, Scotti V, Pisapia P, Cona MS, Rolfo C, Malapelle U, Group IY Abstract Immunotherapy, and in particular immune-checkpoints blockade therapy (ICB), represents a new pillar in cancer therapy. Antibodies targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed Death 1 (PD-1)/Programmed Death Ligand-1 (PD-L1) demonstrated a relevant clinical value in a larg...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Piperno-Neumann Roman-Roman Némati Uveal melanoma (UM) remains without effective therapy at the metastatic stage, which is associated with BAP-1 (BRCA1 associated protein) mutations. However, no data on DNA repair capacities in UM are available. Here, we use UM patient-derived xenografts (PDXs) to study the therapeutic activity of the PARP inhibitor olaparib, alone or in combination. First, we show that the expression and the activity of PARP proteins is similar between the PDXs and the corresponding patient’s tumors. In vivo experiments in the PDX models showed that olaparib was not efficient al...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
The National Cancer Institute has opened a clinical trial using mesothelioma patients and their family members to explore predisposition to the cancer and potential solutions to negating it. The trial is a follow up to an earlier study of a genetic mutation that creates susceptibility to various cancers but a longer-than-normal survival with platinum-based chemotherapy treatment. “This is an important, long-term study that could have implications not only for a patient, but for family members, too,” Dr. Raffit Hassan, NCI senior investigator told The Mesothelioma Center at “Progress can be m...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
CONCLUSIONS: ESS is predominantly seen in male individuals with FST I or II and a history of extensive sun exposure. Histopathologic evaluation shows moderate to severe actinic damage. These individuals frequently have concomitant non-melanoma skin cancer. PMID: 31106645 [PubMed - as supplied by publisher]
Source: Orbit - Category: Opthalmology Authors: Tags: Orbit Source Type: research
This article is protected by copyright. All rights reserved. PMID: 31102460 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
ConclusionsThese two cases suggest that indels might be a new predictor of PD-1 blockade response for ICC patients beside PD-L1 expression, TMB, MSI, and dMMR, warranting further clinical investigation.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
In this study, we reviewed major human studies on the health risks of radiation exposure and showed that sex-related factors may potentially influence the long-term response to radiation exposure. Available data suggest that long-term radiosensitivity in women is higher than that in men who receive a comparable dose of radiation. The report on the biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences, United States emphasized that women may be at significantly greater risk of suffering and dying from radiation-induced cancer than men exposed to the same dose of radiation....
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion and Perspectives Being exquisitely regulated by “writers,” “erasers,” and “readers,” additional repelled proteins or miRNAs, m6A modification relates to nearly any step of mRNA metabolism, as well as ncRNA processing and circRNA translation. There is compelling evidence suggesting that m6A modification is especially critical in a variety of pathologic and physiologic immune responses including T cell homeostasis and differentiation, inflammation, and type I interferon production. Further results have indicated that aberrancies of interferon and Th17 frequencies in systemic lu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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