Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling.
OBJECTIVE
To develop a genome-based classification scheme for clear-cell sarcoma (CCS), also known as melanoma of soft parts (MSP), which would have implications for diagnosis and treatment. This tumor displays characteristic features of soft tissue sarcoma (STS), including deep soft tissue primary location and a characteristic translocation, t(12;22)(q13;q12), involving EWS and ATF1 genes. CCS/MSP also has typical melanoma features, including immunoreactivity for S100 and HMB45, pigmentation, MITF-M expression, and a propensity for regional lymph node metastases.


METHODS
RNA samples from 21 cell lines and 60 pathologically confirmed cases of STS, melanoma, and CCS/MSP were examined using the U95A GeneChip (Affymetrix, Santa Clara, CA). Hierarchical cluster analysis, principal component analysis, and support vector machine (SVM) analysis exploited genomic correlations within the data to classify CCS/MSP.


RESULTS
Unsupervised analyses demonstrated a clear distinction between STS and melanoma and, furthermore, showed that CCS/MSP cluster with the melanomas as a distinct group. A supervised SVM learning approach further validated this finding and provided a user-independent approach to diagnosis. Genes of interest that discriminate CCS/MSP included those encoding melanocyte differentiation antigens, MITF, SOX10, ERBB3, and FGFR1.


CONCLUSIONS
Gene expression profiles support the classification of CCS/MSP as a distinct genomic subtype of melanoma. Analysis of these gene profiles using the SVM may be an important diagnostic tool. Genomic analysis identified potential targets for the development of therapeutic strategies in the treatment of this disease.
Segal
Neil H
NH
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. segaln01@med.nyu.edu.
Pavlidis
Paul
P
Noble
William S
WS
Antonescu
Cristina R
CR
Viale
Agnes
A
Wesley
Umadevi V
UV
Busam
Klaus
K
Gallardo
Humilidad
H
DeSantis
Dianne
D
Brennan
Murray F
MF
Cordon-Cardo
Carlos
C
Wolchok
Jedd D
JD
Houghton
Alan N
AN
D000465:Algorithms; D000951:Antigens, Neoplasm / Q000235:genetics*; D001185:Artificial Intelligence; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D018227:Sarcoma, Clear Cell / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm