The gene expression profile of extraskeletal myxoid chondrosarcoma.
Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumour that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in patients with EMC. In the present study, gene expression profiling has been performed to discover new diagnostic markers and potential therapeutic targets for this tumour type. Global gene expression profiling of ten EMCs and 26 other sarcomas using 42,000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumours profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25% likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top five genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that NMB was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumours and thus could function as a novel diagnostic marker. High levels of expression of PPARG and the gene encoding its interacting protein, PPARGC1A, in most EMCs suggest activation of lipid metabolism pathways in this tumour. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC.
Subramanian
Subbaya
S
Department of Pathology, Stanford University Medical Center, Stanford, CA 94035, USA.
West
Robert B
RB
Marinelli
Robert J
RJ
Nielsen
Torsten O
TO
Rubin
Brian P
BP
Goldblum
John R
JR
Patel
Rajiv M
RM
Zhu
Shirley
S
Montgomery
Kelli
K
Ng
Tony L
TL
Corless
Christopher L
CL
Heinrich
Michael C
MC
van de Rijn
Matt
M
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002813:Chondrosarcoma / Q000235:genetics*; D016000:Cluster Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008870:Microtubules / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009857:Oncogenes / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015287:Neurokinin B; C038393:neuromedin B; D019009:Proto-Oncogene Proteins c-kit