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Breast Cancer Res. 2014 May 20;16(3):210. doi: 10.1186/bcr3658.

Breast cancer intra-tumor heterogeneity.

Author information

1
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. martelol@mskcc.org.
2
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. ngk1@mskcc.org.
3
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. piscuogs@mskcc.org.
4
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. weigeltb@mskcc.org.
5
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. reisfilj@mskcc.org.

Abstract

In recent years it has become clear that cancer cells within a single tumor can display striking morphological, genetic and behavioral variability. Burgeoning genetic, epigenetic and phenomenological data support the existence of intra-tumor genetic heterogeneity in breast cancers; however, its basis is yet to be fully defined. Two of the most widely evoked concepts to explain the origin of heterogeneity within tumors are the cancer stem cell hypothesis and the clonal evolution model. Although the cancer stem cell model appeared to provide an explanation for the variability among the neoplastic cells within a given cancer, advances in massively parallel sequencing have provided several lines of evidence to suggest that intra-tumor genetic heterogeneity likely plays a fundamental role in the phenotypic heterogeneity observed in cancers. Many challenges remain, however, in the interpretation of the next generation sequencing results obtained so far. Here we review the models that explain tumor heterogeneity, the causes of intra-tumor genetic diversity and their impact on our understanding and management of breast cancer, methods to study intra-tumor heterogeneity and the assessment of intra-tumor genetic heterogeneity in the clinic.

PMID:
25928070
PMCID:
PMC4053234
DOI:
10.1186/bcr3658
[Indexed for MEDLINE]
Free PMC Article

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