TY - JOUR
T1 - Frequent genetic differences between matched primary and metastatic breast cancer provide an approach to identification of biomarkers for disease progression
AU - Popławski, Andrzej B
AU - Jankowski, Michał
AU - Erickson, Stephen W
AU - Díaz de Ståhl, Teresita
AU - Partridge, E Christopher
AU - Crasto, Chiquito
AU - Guo, Jingyu
AU - Gibson, John
AU - Menzel, Uwe
AU - Bruder, Carl Eg
AU - Kaczmarczyk, Aneta
AU - Benetkiewicz, Magdalena
AU - Andersson, Robin
AU - Sandgren, Johanna
AU - Zegarska, Barbara
AU - Bała, Dariusz
AU - Srutek, Ewa
AU - Allison, David B
AU - Piotrowski, Arkadiusz
AU - Zegarski, Wojciech
AU - Dumanski, Jan P
PY - 2010/5
Y1 - 2010/5
N2 - Breast cancer is a major cause of morbidity and mortality in women and its metastatic spread is the principal reason behind the fatal outcome. Metastasis-related research of breast cancer is however underdeveloped when compared with the abundant literature on primary tumors. We applied an unexplored approach comparing at high resolution the genomic profiles of primary tumors and synchronous axillary lymph node metastases from 13 patients with breast cancer. Overall, primary tumors displayed 20% higher number of aberrations than metastases. In all but two patients, we detected in total 157 statistically significant differences between primary lesions and matched metastases. We further observed differences that can be linked to metastatic disease and there was also an overlapping pattern of changes between different patients. Many of the differences described here have been previously linked to poor patient survival, suggesting that this is a viable approach toward finding biomarkers for disease progression and definition of new targets useful for development of anticancer drugs. Frequent genetic differences between primary tumors and metastases in breast cancer also question, at least to some extent, the role of primary tumors as a surrogate subject of study for the systemic disease.
AB - Breast cancer is a major cause of morbidity and mortality in women and its metastatic spread is the principal reason behind the fatal outcome. Metastasis-related research of breast cancer is however underdeveloped when compared with the abundant literature on primary tumors. We applied an unexplored approach comparing at high resolution the genomic profiles of primary tumors and synchronous axillary lymph node metastases from 13 patients with breast cancer. Overall, primary tumors displayed 20% higher number of aberrations than metastases. In all but two patients, we detected in total 157 statistically significant differences between primary lesions and matched metastases. We further observed differences that can be linked to metastatic disease and there was also an overlapping pattern of changes between different patients. Many of the differences described here have been previously linked to poor patient survival, suggesting that this is a viable approach toward finding biomarkers for disease progression and definition of new targets useful for development of anticancer drugs. Frequent genetic differences between primary tumors and metastases in breast cancer also question, at least to some extent, the role of primary tumors as a surrogate subject of study for the systemic disease.
KW - Adult
KW - Aged
KW - Breast Neoplasms
KW - Chromosomes, Human, Pair 11
KW - DNA Copy Number Variations
KW - Disease Progression
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation, Neoplastic
KW - Genome, Human
KW - Humans
KW - Lymphatic Metastasis
KW - Middle Aged
KW - Oligonucleotide Array Sequence Analysis
KW - Tumor Markers, Biological
U2 - 10.1038/ejhg.2009.230
DO - 10.1038/ejhg.2009.230
M3 - Journal article
C2 - 20051991
SN - 1018-4813
VL - 18
SP - 560
EP - 568
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 5
ER -
