Molecular characterisation of soft tissue tumours: a gene expression study.
BACKGROUND
Soft-tissue tumours are derived from mesenchymal cells such as fibroblasts, muscle cells, or adipocytes, but for many such tumours the histogenesis is controversial. We aimed to start molecular characterisation of these rare neoplasms and to do a genome-wide search for new diagnostic markers.


METHODS
We analysed gene-expression patterns of 41 soft-tissue tumours with spotted cDNA microarrays. After removal of errors introduced by use of different microarray batches, the expression patterns of 5520 genes that were well defined were used to separate tumours into discrete groups by hierarchical clustering and singular value decomposition.


RESULTS
Synovial sarcomas, gastrointestinal stromal tumours, neural tumours, and a subset of the leiomyosarcomas, showed strikingly distinct gene-expression patterns. Other tumour categories--malignant fibrous histiocytoma, liposarcoma, and the remaining leiomyosarcomas--shared molecular profiles that were not predicted by histological features or immunohistochemistry. Strong expression of known genes, such as KIT in gastrointestinal stromal tumours, was noted within gene sets that distinguished the different sarcomas. However, many uncharacterised genes also contributed to the distinction between tumour types.


CONCLUSIONS
These results suggest a new method for classification of soft-tissue tumours, which could improve on the method based on histological findings. Large numbers of uncharacterised genes contributed to distinctions between the tumours, and some of these could be useful markers for diagnosis, have prognostic significance, or prove possible targets for treatment.
Nielsen
Torsten O
TO
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
West
Rob B
RB
Linn
Sabine C
SC
Alter
Orly
O
Knowling
Margaret A
MA
O'Connell
John X
JX
Zhu
Shirley
S
Fero
Mike
M
Sherlock
Gavin
G
Pollack
Jonathan R
JR
Brown
Patrick O
PO
Botstein
David
D
van de Rijn
Matt
M
D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012509:Sarcoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology