Classification and subtype prediction of adult soft tissue sarcoma by functional genomics.
Adult soft tissue sarcomas are a heterogeneous group of tumors, including well-described subtypes by histological and genotypic criteria, and pleomorphic tumors typically characterized by non-recurrent genetic aberrations and karyotypic heterogeneity. The latter pose a diagnostic challenge, even to experienced pathologists. We proposed that gene expression profiling in soft tissue sarcoma would identify a genomic-based classification scheme that is useful in diagnosis. RNA samples from 51 pathologically confirmed cases, representing nine different histological subtypes of adult soft tissue sarcoma, were examined using the Affymetrix U95A GeneChip. Statistical tests were performed on experimental groups identified by cluster analysis, to find discriminating genes that could subsequently be applied in a support vector machine algorithm. Synovial sarcomas, round-cell/myxoid liposarcomas, clear-cell sarcomas and gastrointestinal stromal tumors displayed remarkably distinct and homogenous gene expression profiles. Pleomorphic tumors were heterogeneous. Notably, a subset of malignant fibrous histiocytomas, a controversialhistological subtype, was identified as a distinct genomic group. The support vector machine algorithm supported a genomic basis for diagnosis, with both high sensitivity and specificity. In conclusion, we showed gene expression profiling to be useful in classification and diagnosis, providing insights into pathogenesis and pointing to potential new therapeutic targets of soft tissue sarcoma.
Segal
Neil H
NH
Swim Across America Laboratory, Department of Surgery, Memorial-Sloan Kettering Cancer Center, New York and Columbia Genome Center, Columbia University, New York, New York 10021, USA. segaln01@med.nyu.edu
Pavlidis
Paul
P
Antonescu
Cristina R
CR
Maki
Robert G
RG
Noble
William S
WS
DeSantis
Diann
D
Woodruff
James M
JM
Lewis
Jonathan J
JJ
Brennan
Murray F
MF
Houghton
Alan N
AN
Cordon-Cardo
Carlos
C
D000328:Adult; D000465:Algorithms; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012509:Sarcoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology