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Arsenic in drinking water is one of the major etiological factors in urinary bladder carcinoma (BlCa). Here, high-resolution CGH-SNP microarray analysis in arsenic accumulated BlCa tissues showed significant (p < 0.05) association of chromosomal alterations with high arsenic (≥112 ng/g) accumulation, further corroborated by high γH2AX nuclear expression. Cytobands 5q11-35, 9p24.3-21.5, 18q11.1-25, etc. showed deletion, whereas 12q was amplified in high arsenic samples (AsH). Consecutively, IPA® found FA-BRCA pathway to be exclusively altered in AsH group. Validation of several key regulatory genes (RAD50, BRIP1, UIMC1, FANCD2, BRCA2 and BRCA1) of the pathway, were performed in independent BlCa cases (n = 81). UIMC1, RAD50 and BRIP1 were differentially deleted and associated with poor survival of AsH samples. Moreover, reduced nuclear expression with diffused cytoplasmic expression of FANCD2 was higher in AsH samples. Collectively, frequent deregulation of RAD50, UIMC1 and BRIP1 may result in reduced nuclear translocation of FANCD2, which may cause more chromosomal aberrations among AsH samples.
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http://dx.doi.org/10.1016/j.ygeno.2020.09.012 | DOI Listing |
Cell Death Discov
July 2025
Novocure LTD, Haifa, Israel.
Tumor Treating Fields (TTFields) therapy is an approved cancer treatment modality, based on non-invasive application of electric fields to the tumor region. Proteomic and cell biology methods revealed a versatile mechanism of action to be involved in the response to TTFields. In the current research we performed whole transcriptome analysis across tumor types to identify pan-cancer responses to TTFields.
View Article and Find Full Text PDFJ Clin Invest
June 2025
Department of Human Genetics, Biozentrum, University of Wurzburg, Wurzburg, Germany.
The Fanconi anemia/breast cancer (FA/BRCA) DNA repair network promotes the removal of DNA interstrand crosslinks (ICLs) to counteract their devastating consequences, including oncogenesis. Network signaling is initiated by the FA core complex, which consists of 7 authentic FA proteins and an FA-associated protein, FAAP100, with incompletely characterized roles and unknown disease associations. Upon activation, the FA core complex functions as a multiprotein E3 ubiquitin ligase centered on its catalytic module, the FANCB-FANCL-FAAP100 (BLP100) subcomplex, for FANCD2 and FANCI monoubiquitylation.
View Article and Find Full Text PDFExp Ther Med
March 2025
Human Genetics Institute 'Dr Enrique Corona Rivera', Department of Molecular Biology and Genomics, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco 44340, México.
Fanconi anemia (FA) is the most common hereditary bone marrow failure syndrome, with an incidence of 1 in 5,000,000. This disease is caused by an alteration in one of the 23 genes associated with the FA/BRCA DNA repair pathway, which is responsible for repairing interstrand bridges generated during homologous recombination. FA has been associated with a predisposition to other types of neoplasm.
View Article and Find Full Text PDFNat Commun
August 2024
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Mol Cell
July 2024
Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Medical Oncology, Da
The twenty-three Fanconi anemia (FA) proteins cooperate in the FA/BRCA pathway to repair DNA interstrand cross-links (ICLs). The cell division cycle and apoptosis regulator 1 (CCAR1) protein is also a regulator of ICL repair, though its possible function in the FA/BRCA pathway remains unknown. Here, we demonstrate that CCAR1 plays a unique upstream role in the FA/BRCA pathway and is required for FANCA protein expression in human cells.
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