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Title:
Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases | Breast Cancer Research and Treatment
Description:
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.
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Keywords {🔍}
cancer, breast, google, scholar, article, pubmed, cas, genomic, primary, clonal, carcinomas, heterogeneity, metastases, teixeira, genetic, patients, lymph, comparative, analysis, hybridization, res, node, tumors, chromosomes, pandis, intratumor, heim, tissue, tumor, genes, normal, pathol, privacy, cookies, content, research, divergence, manuel, samples, access, dna, publish, search, torres, ribeiro, median, number, imbalances, cell, prognostic,
Topics {✒️}
month download article/chapter node-negative breast cancer rikshospitalet-radiumhospitalet medical center intratumor genomic heterogeneity comparative genomic hybridization paired primary-metastatic samples breast cancer metastasis primary breast cancers lymph node metastases comparative genomic hybridisation full article pdf hierarchical clustering analysis tumor cell populations breast cancer patients privacy choices/manage cookies metastasis-free survival dna stemline heterogeneity human breast cancer metastatic breast cancer breast cancer polyclonality teixeira mr primary breast carcinomas nonmalignant breast tissue disparate clonal populations normal breast tissue flow cytometric analysis norwegian cancer society genomic imbalances detected tumor heterogeneity extra-tumorous samples related subjects portuguese oncology institute genetic aberrations detected european economic area world health organization standard reference intervals s-phase fraction combined chromosome banding liga portuguesa contra saint savas hospital breast carcinoma revealed normal tissue adjacent dna sequence losses conditions privacy policy clonal heterogeneity article torres genetic heterogeneity epithelial carcinogenesis disagree intratumor variability asynchronous metastasis
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headline:Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases
description: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.
datePublished:2006-08-09T00:00:00Z
dateModified:2006-08-09T00:00:00Z
pageStart:143
pageEnd:155
sameAs:https://doi.org/10.1007/s10549-006-9317-6
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Breast cancer
Comparative genomic hybridization
Intratumor genetic heterogeneity
Primary tumor
Lymph node metastasis
Oncology
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headline:Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases
description: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.
datePublished:2006-08-09T00:00:00Z
dateModified:2006-08-09T00:00:00Z
pageStart:143
pageEnd:155
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Breast cancer
Comparative genomic hybridization
Intratumor genetic heterogeneity
Primary tumor
Lymph node metastasis
Oncology
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