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. 2015 Jan 15:4:23.
doi: 10.1186/s40064-015-0787-z. eCollection 2015.

ATM gene mutations in sporadic breast cancer patients from Brazil

Flavia Rotea Mangone  1 , Elisabete C Miracca  1 , Harriet E Feilotter  2 , Lois M Mulligan  3 , Maria Aparecida Nagai  4
Affiliations

ATM gene mutations in sporadic breast cancer patients from Brazil

Flavia Rotea Mangone et al. Springerplus. .

Abstract

Purpose: The Ataxia-telangiectasia mutated (ATM) gene encodes a multifunctional kinase, which is linked to important cellular functions. Women heterozygous for ATM mutations have an estimated relative risk of developing breast cancer of 3.8. However, the pattern of ATM mutations and their role in breast cancer etiology has been controversial and remains unclear. In the present study, we investigated the frequency and spectrum of ATM mutations in a series of sporadic breast cancers and controls from the Brazilian population.

Methods: Using PCR-Single Strand Conformation Polymorphism (SSCP) analysis and direct DNA sequencing, we screened a panel of 100 consecutive, unselected sporadic breast tumors and 100 matched controls for all 62 coding exons and flanking introns of the ATM gene.

Results: Several polymorphisms were detected in 12 of the 62 coding exons of the ATM gene. These polymorphisms were observed in both breast cancer patients and the control population. In addition, evidence of potential ATM mutations was observed in 7 of the 100 breast cancer cases analyzed. These potential mutations included six missense variants found in exon 13 (p.L546V), exon 14 (p.P604S), exon 20 (p.T935R), exon 42 (p.G2023R), exon 49 (p.L2307F), and exon 50 (p.L2332P) and one nonsense mutation in exon 39 (p.R1882X), which was predicted to generate a truncated protein.

Conclusions: Our results corroborate the hypothesis that sporadic breast tumors may occur in carriers of low penetrance ATM mutant alleles and these mutations confer different levels of breast cancer risk.

Keywords: ATM gene; Breast cancer; Mutations; Polymorphisms.

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Figures

Figure 1
Figure 1
ATM nonsense mutation in a sporadic breast cancer patient. A, SSCP analysis of exon 39 (case M115); B, sequence profile for exon 39 showing a nonsense mutation R1882X; C, loss of heterozygosity at marker D11S1818; N, normal DNA; T, tumor DNA.
Figure 2
Figure 2
Representative examples of the sequencing analysis of potential ATM mutations in sporadic breast cancer patients. A, upper panel: reference sequence; B, middle panel: sequencing electropherograms from normal tissue samples from breast cancer patients (227 N, 231 N, 214 N, and 72NL); C, lower panel: sequencing electropherograms from tumor tissue samples from breast cancer patients (227 T, 231 T, 214 T, and 72TL). Case 227 showed two potential ATM missense mutations without evidence of LOH; Cases 214 and 231 showed potential ATM mutations with evidence of loss of the wild type allele.
See this image and copyright information in PMC

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