Five- hit hypothesis in ATM gene: An individualized model in a breast cancer patient.

Five- hit hypothesis in ATM gene: An individualized model in a breast cancer patient. Front Biosci (Elite Ed). 2018 Mar 01;10:375-383 Authors: Mehdipour P, Azarnezhad A Abstract The aim of this study was to trace D1853N in a proband affected with primary BC to explore the molecular, cellular and structural aspects of ATM. Exon 37 and splicing regions were PCR-sequenced. Allelic location of the alterations was determined by molecular cloning. Possible impact of alterations was investigated through the bioinformatics and protein expression assays. Five genetic variants including IVS 36-91 AA>TT, IVS 36-8 T>C, D1853N, IVS 37+47 A>G, IVS 37+60 Del T were found in the target regions of ATM and all the alterations were occurred heterezygously. IVS 36-8 T>C and D1853N were observed in blood and tumor tissue, whilst splicing variants were only occurred in tumor tissue. Missense D1853N alteration seems to be effective on 2D and 3D structure of ATM protein and the probability of splicing found to be decreased by intronic variants. Protein expression of ATM also confirmed the occurrence and functional impact of alterations. Results reflect a five-hit hypothesis in a proband with BC that influence ATM, as a guard of genomic stability, at molecular, cellular, and structural levels. PMID: 29293464 [PubMed - in process]
Source: Frontiers in Bioscience - Elite - Category: Biomedical Science Tags: Front Biosci (Elite Ed) Source Type: research

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