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Molecular Basis of BRCA1 and BRCA2: Homologous Recombination Deficiency and Tissue-Specific Carcinogenesis

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Hereditary Breast and Ovarian Cancer

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Abstract

Mutations in BRCA1 and BRCA2 cause hereditary breast and ovarian cancer (HBOC) syndrome, and these genes play multiple critical roles in maintaining genomic stability. One particularly important function of these genes is the homologous recombination (HR) repair of DNA. HR repair is an essential error-free repair mechanism for DNA double-strand breaks that utilizes an intact sister chromatid as a template. In addition to its role in HBOC oncogenesis, HR dysfunction is a target for treatment with poly (ADP-ribose) polymerase (PARP) inhibitors. Germline mutations of BRCA1/BRCA2 cause breast, ovarian, fallopian tube, and peritoneal cancers with high rates of genomic alterations accompanied by poor prognoses. The mechanism underlying this tissue specificity has not yet clearly been explained, but several studies have examined its possible association with estrogen signaling. In this review, we first introduced the molecular mechanisms of HR mediated by BRCA1 and BRCA2 in the context of PARP inhibitor sensitivity. We also discussed several hypotheses describing estrogen- and HR deficiency-dependent genomic instability. Understanding these mechanisms is crucial for the adequate treatment and prevention of HBOC-related cancers.

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  1. Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, Japan

    Tomohiko Ohta & Wenwen Wu

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  1. Tomohiko Ohta
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  2. Wenwen Wu
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Correspondence to Tomohiko Ohta .

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  1. Department of Breast Surgical Oncology, Showa University, School of Medicine, Tokyo, Japan

    Seigo Nakamura

  2. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan

    Daisuke Aoki

  3. Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    Yoshio Miki

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Ohta, T., Wu, W. (2021). Molecular Basis of BRCA1 and BRCA2: Homologous Recombination Deficiency and Tissue-Specific Carcinogenesis. In: Nakamura, S., Aoki, D., Miki, Y. (eds) Hereditary Breast and Ovarian Cancer . Springer, Singapore. https://doi.org/10.1007/978-981-16-4521-1_2

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  • DOI: https://doi.org/10.1007/978-981-16-4521-1_2

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  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-16-4520-4

  • Online ISBN: 978-981-16-4521-1

  • eBook Packages: MedicineMedicine (R0)

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