TY - JOUR
T1 - Frequent genetic differences between matched primary and metastatic breast cancer provide an approach to identification of biomarkers for disease progression
AU - Popawski, Andrzej B.
AU - Jankowski, Micha
AU - Erickson, Stephen W.
AU - Díaz De Sthl, 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 - Baa, Dariusz
AU - Śrutek, Ewa
AU - Allison, David B.
AU - Piotrowski, Arkadiusz
AU - Zegarski, Wojciech
AU - Dumanski, Jan P.
N1 - Funding Information:
We thank Drs Eva Tiensuu Janson and Devin Absher for a critical review of the manuscript. This study was supported by the University of Alabama at Birmingham, the Swedish Cancer Foundation and the Swedish Children Cancer Fund. SWE was supported by NIH grant T32 HL072757.
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 - Amplification
KW - Array-CGH
KW - Deletion
KW - Gain
KW - Oncogenes
KW - Tumor suppressor genes
UR - http://www.scopus.com/inward/record.url?scp=77951620282&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2009.230
DO - 10.1038/ejhg.2009.230
M3 - Article
C2 - 20051991
AN - SCOPUS:77951620282
SN - 1018-4813
VL - 18
SP - 560
EP - 568
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 5
ER -