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

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Torres, L (Author) Other; Ribeiro, FR (Author) Other; Pandis, N (Author) Other; Andersen, JA (Author) Other; Heim, S (Author) Other; Manuel R Teixeira (Author) ICBAS

Journal

Title: Breast Cancer Research and Treatment

Vol. 102

Pages: 143-155

ISSN: 0167-6806

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 120 Citations

Scopus - 129 Citations

Other information

Authenticus ID: P-004-AR9

DOI: 10.1007/s10549-006-9317-6

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13