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Human Genetics

, Volume 132, Issue 8, pp 845–863 | Cite as

The complex genetic landscape of familial breast cancer

  • Lorenzo MelchorEmail author
  • Javier Benítez
Review Paper

Abstract

Familial breast cancer represents a minor percentage of all human breast cancers. Mutations in two high susceptibility genes BRCA1 and BRCA2 explain around 25 % of familial breast cancers, while other high, moderate and low susceptibility genes explain up to 20 % more of breast cancer families. Thus, it is important to decipher the genetic architecture of families that show no mutations to improve genetic counselling. The comprehensive description of familial breast cancer using different techniques and platforms has shown to be very valuable for better patient diagnosis, tumour surveillance, and ultimately patient treatment. This review focuses on the complex landscape of pathological, protein, genetic and genomic features associated with BRCA1-, BRCA2-, and non-BRCA1/BRCA2-related cancers described up to date. Special emphasis deserves the coexistence of distinct molecular breast cancer subtypes, the development of tumour classifiers to predict BRCA1/2 mutations, and the last insights from recent whole genome sequencing studies and miRNA profiling.

Keywords

Breast Cancer TP53 Mutation Familial Breast Cancer Sporadic Breast Cancer BRCA1 Promoter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

aCGH

Array-based comparative genomic hybridisation

BC

Breast cancer

cCGH

Conventional or chromosomal-based comparative genomic hybridisation

DSB

Double strand break DNA

ER

Oestrogen receptor

FBC

Familial breast cancer

GAP

Genomic aberration pattern

GEP

Gene expression profile

HR

Homologous recombination DNA repair

IHC

Immunohistochemistry or immunohistochemical

MLPA

Multiplex ligation-dependent probe amplification

NGS

Next generation sequencing

NHEJ

Non-homologous end joining DNA repair

PR

Progesterone receptor

SBC

Sporadic breast cancer

TNBL

Triple-negative basal-like breast cancers

Notes

Acknowledgments

The authors would like to thank all members of the Human Genetics Team for the last 10 years, who have been key in our advance in understanding familial breast cancer. We are grateful to the financial support from FIS PI12/0070 and INNPRONTA (MICIN) programmes.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Human Genetics Group, Programme of Human Cancer GeneticsSpanish National Cancer Research Centre (CNIO)MadridSpain
  2. 2.Haemato-oncology Research Unit, Division of Molecular PathologyThe Institute of Cancer ResearchSuttonUK
  3. 3.Biomedical Network on Rare Diseases (CIBERER)MadridSpain

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