Gene expression profiling of synovial sarcoma: distinct signature of poorly differentiated type.
Poorly differentiated type synovial sarcoma (PDSS) is a variant of synovial sarcoma characterized by predominantly round or short-spindled cell morphology. Although accumulating evidence from clinicopathologic studies suggests a strong association between this variant of synovial sarcoma and poor prognosis, little has been reported on the molecular basis of PDSS. To gain insights into the mechanism(s) that underlie the emergence of PDSS, we analyzed the gene expression profiles of 34 synovial sarcoma clinical samples, including 5 cases of PDSS, using an oligonucleotide microarray. In an unsupervised analysis, the 34 samples fell into 3 groups that correlate closely with histologic subtypes: monophasic, biphasic, and poorly differentiated types. PDSS was characterized by down-regulation of genes associated with neuronal and skeletal development and cell adhesion. Moreover, upregulation of genes on a specific chromosomal locus, 8q21.11, was identified. This locus-specific transcriptional activation in PDSS was confirmed by reverse transcriptase-PCR analysis of 9 additional synovial sarcoma samples. Our results indicate that PDSS tumors constitute a distinct group based on expression profiles.
Genetics Division, National Cancer Center Research Institute, Keio University School of Medicine , Tokyo, Japan.
Robert
R
Nakayama
Sachiyo
S
Mitani
Takeshi
T
Nakagawa
Tadashi
T
Hasegawa
Akira
A
Kawai
Hideo
H
Morioka
Hiroo
H
Yabe
Yoshiaki
Y
Toyama
Akira
A
Ogose
Junya
J
Toguchida
Tomitaka
T
Nakayama
Teruhiko
T
Yoshida
Hitoshi
H
Ichikawa
D002454:Cell Differentiation / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000145:classification / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000145:classification / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013997:Time Factors