Identification of brain- and bone-specific breast cancer metastasis genes.
In breast cancer, metastases are relatively widely distributed, with the most common sites being bone, regional lymph nodes, lung, liver, and brain. The detailed mechanism of organ-specific metastasis is poorly understood. In this study, we initiated a search for genes that are implicated in brain or bone metastasis of primary human breast cancer. We generated gene expression profiles of 18 brain and eight bone metastases derived from primary breast tumors. We identified 73 genes differentially expressed between brain and bone metastases. Visualization of the differential gene expression profiles by correspondence and cluster analyses shows that the metastases clearly separate into two distinct groups as an exact reflection of their site of metastasis. Moreover, the analysis of this gene set in primary breast tumors relapsing to either bone or brain allowed accurate categorization of the tumors according to their metastatic site. The identified genes may prove to be excellent markers to predict the site of metastasis in breast cancer patients and could lead to tailor-made therapy to an individual patient.
Klein
Andreas
A
Institute of Molecular Biology and Bioinformatics, Charité, Campus Benjamin Franklin, Arnimalle 22, Berlin, Germany. andreas.klein@charite.de
Olendrowitz
Christian
C
Schmutzler
Rita
R
Hampl
Juergen
J
Schlag
Peter M
PM
Maass
Nicolai
N
Arnold
Norbert
N
Wessel
Ralf
R
Ramser
Juliane
J
Meindl
Alfons
A
Scherneck
Siegfried
S
Seitz
Susanne
S
D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary*; D001932:Brain Neoplasms / Q000235:genetics / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D060588:LIM Domain Proteins; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009928:Organ Specificity
C486181:CRIP1 protein, human; D002352:Carrier Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D060588:LIM Domain Proteins; C446297:LRRC15 protein, human; D008565:Membrane Proteins; D053509:Matrix Metalloproteinase 13