IMR Press / FBE / Volume 10 / Issue 2 / DOI: 10.2741/E828

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

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

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1 Department of Medical genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

*Author to whom correspondence should be addressed.

Front. Biosci. (Elite Ed) 2018, 10(2), 375–383; https://doi.org/10.2741/E828
Published: 1 March 2018
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.

Keywords
Ataxia Telangiectasia Mutated
Polymorphism
Breast cancer
hit- hypothesis
Evolution
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