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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

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

Revista

Título: Breast Cancer Research and Treatment

Vol. 102

Páginas: 143-155

ISSN: 0167-6806

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 120 Citações

Scopus - 129 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13