[Frontiers in Bioscience E4, 934-949, January 1, 2012]

Genetic and epigenetic signatures of breast cancer subtypes

Shane R. Stecklein1, Roy A. Jensen1, Arindam Pal1

1Department of Pathology and Laboratory Medicine and The University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Breast Cancer Stem Cells
4. Intrinsic Subtypes of Breast Cancer
4.1. Tumors arising from luminally-committed cells
4.1.1. Luminal A and luminal B Tumors
4.1.2. ERBB2/HER2 Tumors
4.2. The luminal progenitor ("basal-like") cancers
4.3. Tumors arising from transformation of the mammary stem cell
5. Genetic Risk Factors for Breast Cancer: BRCA1 and the basal-like phenotype
6. Epigenetic Changes in Breast Cancer Subtypes
6.1. DNA methylation
6.2. Histone modifications
6.3. MicroRNAs (miRNAs)
7. Final comments
8. Acknowledgements
9. References

1. ABSTRACT

Breast cancer is a heterogeneous disease at both the histological and molecular levels. The current model of breast tumorigenesis suggests that the normal mammary stem cell and the various progenitors that arise thereof can be transformed and generate lineage-restricted tumor phenotypes. This model is supported by observations that the different subtypes of breast cancer share transcriptional signatures intrinsic to normal components of the mammary epithelium. Studies have since elaborated these molecular signatures to include recurrent genetic abnormalities, patterns of DNA methylation and dysregulation of microRNAs. Here we aim to review the current state of knowledge concerning the cellular etiology of breast cancer subtypes and the genetic, transcriptional and epigenetic aberrations associated with each subtype.