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Double heterozygous mutation in the BRCA1 and ATM genes involved in development of primary metachronous tumours: a case report

  • Raquel AndrésEmail author
  • Sebastian Menao
  • María Arruebo
  • Elisa Quílez
  • Maria José Cardiel
Brief Report
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Abstract

Purpose

Between 5 and 10% of cases of breast cancer (BC) are attributable to a genetic susceptibility. The BRCA1 and BRCA2 genes described in the late 1990s are associated with an increased risk of breast and ovarian cancer, and the clinical management of carriers of pathogenic variants in these genes is defined in several clinical guidelines (Paluch-Shimon et al. in Ann Oncol 27(suppl 5):v103–v110, 2016; Llort et al. in Clin Transl Oncol 17(12):956–961, 2015). However, the pathogenic variants in BRCA1 and BRCA2 represent only a third of the causes of hereditary BC (Easton et al. in N Engl J Med 372:2243–2257, 2015). The incorporation of NGS (Next Generation Sequencing) techniques in the genetic diagnosis of this pathology, in addition to minimising the cost and time of analysis, allows the simultaneous study of other genes of high and moderate penetrance (Easton et al. in N Engl J Med 372:2243–2257, 2015; Op. Cit.; Tung et al. in Cancer 121(1):25–33, 2015). To date, there are not many cases or series of patients that describe the co-occurrence of two pathogenic variants in these genes of BC. Cases of double heterozygosis have been described with the presence of pathogenic variants in BRCA1, BRCA2, PALB2, CHEK2, BLM or NBN (Nomizu et al. in Breast Cancer 22(5):557–61, 2015; Heidemann et al. in Breast Cancer Res Treat 134(3):1229–1239, 2012; Zuradelli et al. in Breast Cancer Res Treat 124(1):251–258, 2010; Sokolenko et al. in Breast Cancer Res Treat 145(2):553–562, 2014).

Methods

We report the case of a patient diagnosed with multiple tumours who presented two pathogenic variants in heterozygosis.

Results

Two pathogenic variants, c.5123C > A (p.Ala1708Glu) in the BRCA1 gene and c.2413C > T (p.Arg805X) in the ATM gene were detected in heterozygosis. Said variants were confirmed by Sanger-type sequencing using specific primers.

Conclusions

The implementation of gene panels using NGS in the study of hereditary cancer involves the detection of heterozygous double mutations in genes of high and moderate penetrance for cancer, although with a low frequency.

Keywords

ATM BRCA1 Breast cancer Double heterocygote 

Notes

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Hospital Clínico Universitario Lozano BlesaZaragozaSpain

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