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Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases.

Abstract：

:Conflicting theories of epithelial carcinogenesis disagree on the clonal composition of primary tumors and on the time at which metastases occur. In order to study the spatial distribution of disparate clonal populations within breast carcinomas and the extent of the genetic relationship between primary tumors and regional metastases, we have analyzed by comparative genomic hybridization 122 tissue samples from altogether 60 breast cancer patients, including 34 tumor samples obtained from different quadrants of 9 breast carcinomas, as well as paired primary-metastatic samples from 12 patients. The median intratumor genetic heterogeneity score (HS) was 17.4% and unsupervised hierarchical clustering analysis comparing the genetic features to those of an independent series of 41 breast carcinomas confirmed intratumor clonal divergence in a high proportion of cases. The median HS between paired primary breast tumors and lymph node metastases was 33.3%, but the number of genomic imbalances did not differ significantly. Clustering analysis confirmed extensive clonal divergence between primary carcinomas and lymph node metastases in several cases. In the independent series of 41 breast carcinomas, the number of genomic imbalances in primary tumors was significantly higher in patients presenting lymph node metastases (median = 15.5) than in the group with no evidence of disease spreading at diagnosis (median = 5.0). We conclude that primary breast carcinomas may be composed of several genetically heterogeneous and spatially separated cell populations and that paired primary breast tumors and lymph node metastases often present divergent clonal evolution, indicating that metastases may occur relatively early during breast carcinogenesis.

journal_name

Breast Cancer Res Treat

journal_title

Breast cancer research and treatment

authors

Torres L,Ribeiro FR,Pandis N,Andersen JA,Heim S,Teixeira MR

doi

10.1007/s10549-006-9317-6

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

143-55

issue

eissn

0167-6806

issn

1573-7217

journal_volume

102

pub_type

杂志文章

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Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases.