Gene expression patterns and gene copy number changes in dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans (DFSP) is an aggressive spindle cell neoplasm. It is associated with the chromosomal translocation, t(17:22), which fuses the COL1A1 and PDGFbeta genes. We determined the characteristic gene expression profile of DFSP and characterized DNA copy number changes in DFSP by array-based comparative genomic hybridization (array CGH). Fresh frozen and formalin-fixed, paraffin-embedded samples of DFSP were analyzed by array CGH (four cases) and DNA microarray analysis of global gene expression (nine cases). The nine DFSPs were readily distinguished from 27 other diverse soft tissue tumors based on their gene expression patterns. Genes characteristically expressed in the DFSPs included PDGF beta and its receptor, PDGFRB, APOD, MEOX1, PLA2R, and PRKCA. Array CGH of DNA extracted either from frozen tumor samples or from paraffin blocks yielded equivalent results. Large areas of chromosomes 17q and 22q, bounded by COL1A1 and PDGF beta, respectively, were amplified in DFSP. Expression of genes in the amplified regions was significantly elevated. Our data shows that: 1) DFSP has a distinctive gene expression profile; 2) array CGH can be applied successfully to frozen or formalin-fixed, paraffin-embedded tumor samples; 3) a characteristic amplification of sequences from chromosomes 17q and 22q, demarcated by the COL1A1 and PDGF beta genes, respectively, was associated with elevated expression of the amplified genes.
Linn
Sabine C
SC
Departments of Pathology, Genetics, and Biochemistry, and Howard Hughes Medical Institute, Stanford University Medical Center, Stanford, California 94305, USA.
West
Rob B
RB
Pollack
Jonathan R
JR
Zhu
Shirley
S
Hernandez-Boussard
Tina
T
Nielsen
Torsten O
TO
Rubin
Brian P
BP
Patel
Rajiv
R
Goldblum
John R
JR
Siegmund
David
D
Botstein
David
D
Brown
Patrick O
PO
Gilks
C Blake
CB
van de Rijn
Matt
M
D000328:Adult; D000368:Aged; D015925:Cryopreservation; D018223:Dermatofibrosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016707:Tissue Fixation
D005404:Fixatives; D005557:Formaldehyde