Frequent genetic differences between matched primary and metastatic breast cancer provide an approach to identification of biomarkers for disease progression.
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.
Popławski
Andrzej B
AB
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
Jankowski
Michał
M
Erickson
Stephen W
SW
Díaz de Ståhl
Teresita
T
Partridge
E Christopher
EC
Crasto
Chiquito
C
Guo
Jingyu
J
Gibson
John
J
Menzel
Uwe
U
Bruder
Carl Eg
CE
Kaczmarczyk
Aneta
A
Benetkiewicz
Magdalena
M
Andersson
Robin
R
Sandgren
Johanna
J
Zegarska
Barbara
B
Bała
Dariusz
D
Srutek
Ewa
E
Allison
David B
DB
Piotrowski
Arkadiusz
A
Zegarski
Wojciech
W
Dumanski
Jan P
JP
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis
D014408:Biomarkers, Tumor