ATM gene mutations in sporadic breast cancer patients from Brazil

Mangone, Flávia Rotea; Miracca, Elisabete; Feilotter, Harriet; Mulligan, Lois M.; Nagai, María Aparecida

doi:10.1186/s40064-015-0787-z

Cited by 18 publications

(13 citation statements)

References 79 publications

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“…Patients with germline variants in ATM (P604S) and SMO (R400H) were diagnosed with melanoma at ages significantly younger than the average of all included patients (35 and 42). Heterozygous missense mutations in ATM, including the variant identified in our study, have been postulated to increase the risk for breast cancer and aggressive Hodgkin's lymphoma (Liberzon et al, 2004;Mangone et al, 2015;Offit et al, 2002). An 80-year-old patient was found to have a germline mutation in MLH1 (S406N), a gene implicated in Lynch syndrome.…”

Section: Discussionmentioning

confidence: 66%

Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure

Haugh

Zhang

Quan

et al. 2018

Journal of Investigative Dermatology

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Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n = 21), volar (n = 9), and subungual/interdigital (n = 13) acral skin as well as acral nevi (n = 24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared with volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (P = 0.01), were significantly less likely to have the superficial spreading histologic subtype (P = 0.01), occurred in older patients (P = 0.05), and had more frequent involvement in non-Caucasians (P = 0.01). These differences can be explained by differing levels of UV exposure. Subungual/interdigital melanomas had the most diverse group of oncogenic mutations including PIK3CA (2/13), STK11 (2/13), EGFR (1/13), FGFR3 (1/13), and PTPN11 (1/13). In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67%) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. Although based on a limited sample size, differences between volar and subungual/interdigital melanomas in our study may be the result of differing levels of UV exposure.

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Section: Discussionmentioning

confidence: 66%

Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure

Haugh

Zhang

Quan

et al. 2018

Journal of Investigative Dermatology

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“…Mutation c.6067G > A was observed in a patient from Brazil with sporadic breast cancer. In that case, the tumor was diagnosed at the age of 45 and was defined as clinical stage II [ 32 ]. In our case tumor was diagnosed at the age of 49 and the pathologic stage of tumor was defined as T2N1M0.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in ATM, H2AFX and MRE11 genes and susceptibility to breast cancer in the polish population

et al. 2018

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BackgroundDNA damage repair is a complex process, which can trigger the development of cancer if disturbed. In this study, we hypothesize a role of variants in the ATM, H2AFX and MRE11 genes in determining breast cancer (BC) susceptibility.MethodsWe examined the whole sequence of the ATM kinase domain and estimated the frequency of founder mutations in the ATM gene (c.5932G > T, c.6095G > A, and c.7630-2A > C) and single nucleotide polymorphisms (SNPs) in H2AFX (rs643788, rs8551, rs7759, and rs2509049) and MRE11 (rs1061956 and rs2155209) among 315 breast cancer patients and 515 controls. The analysis was performed using high-resolution melting for new variants and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for recurrent ATM mutations. H2AFX and MRE11 polymorphisms were analyzed using TaqMan assays. The cumulative genetic risk scores (CGRS) were calculated using unweighted and weighted approaches.ResultsWe identified four mutations (c.6067G > A, c.8314G > A, c.8187A > T, and c.6095G > A) in the ATM gene in three BC cases and two control subjects. We observed a statistically significant association of H2AFX variants with BC. Risk alleles (the G of rs7759 and the T of rs8551 and rs2509049) were observed more frequently in BC cases compared to the control group, with P values, odds ratios (OR) and 95% confidence intervals (CIs) of 0.0018, 1.47 (1.19 to 1.82); 0.018, 1.33 (1.09 to 1.64); and 0.024, 1.3 (1.06 to 1.59), respectively. Haplotype-based tests identified a significant association of the H2AFX CACT haplotype with BC (P < 0.0001, OR = 27.29, 95% CI 3.56 to 209.5). The risk of BC increased with the growing number of risk alleles. The OR (95% CI) for carriers of ≥ four risk alleles was 1.71 (1.11 to 2.62) for the CGRS.ConclusionsThis study confirms that H2AFX variants are associated with an increased risk of BC. The above-reported sequence variants of MRE11 genes may not constitute a risk factor of breast cancer in the Polish population. The contribution of mutations detected in the ATM gene to the development of breast cancer needs further detailed study.

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“…We performed a PubMed search (up to February 10, ) of the following keywords in the title/abstract of the articles: [‘‘ATM’’] AND [‘‘penetrance’’ OR ‘‘risk’’] AND [‘‘breast’’]. Additional studies were identified by a manual search of references from original articles and reviews.…”

Section: Methodsmentioning

confidence: 99%

Penetrance of ATM Gene Mutations in Breast Cancer: A Meta‐Analysis of Different Measures of Risk

Marabelli

Cheng

Parmigiani

2016

Genetic Epidemiology

118

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The gene responsible for ataxia-telangiectasia syndrome, ATM, is also an intermediate-risk breast cancer (BC) susceptibility gene. Numerous studies have been carried out to determine the contribution of ATM gene mutations to BC risk. Epidemiological cohorts, segregation analyses, and case-control studies reported BC risk in different forms, including penetrance, relative risk, standardized incidence ratio, and odds ratio. Because the reported estimates vary both qualitatively and quantitatively, we developed a general model allowing the integration of the different types of cancer risk available in the literature. We performed a comprehensive meta-analysis identifying 19 studies, and used our model to obtain a consensus estimate of BC penetrance. We estimated the cumulative risk of BC in heterozygous ATM mutation carriers to be 6.02% by 50 years of age (95% credible interval: 4.58-7.42%) and 32.83% by 80 years of age (95% credible interval: 24.55-40.43%). An accurate assessment of cancer penetrance is crucial to help mutation carriers make medical and lifestyle decisions that can reduce their chances of developing the disease.

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ATM gene mutations in sporadic breast cancer patients from Brazil

Cited by 18 publications

References 79 publications

Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure

Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure

Genetic variants in ATM, H2AFX and MRE11 genes and susceptibility to breast cancer in the polish population

Penetrance of ATM Gene Mutations in Breast Cancer: A Meta‐Analysis of Different Measures of Risk

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