Frequent deletion of CDKN2A and recurrent coamplification of KIT, PDGFRA, and KDR in fibrosarcoma of bone--an array comparative genomic hybridization study.
Very little is known about the genetics of fibrosarcoma (FS) of bone. We applied array comparative genomic hybridization (CGH) to identify genes and genomic regions with potential role in the pathogenesis of this tumor. Seventeen patients with FS of bone were included in the study. Array CGH analysis was carried out in 13 fresh frozen tissue specimens from 11 of these patients (nine primary tumors and four local recurrences). DNA was extracted and hybridizations were performed on Agilent 244K CGH oligoarrays. The data were analyzed using Agilent DNA Analytics Software. The number of changes per patient ranged from 0 to 132 (average = 43). Losses were most commonly detected at 6q, 8p, 9p, 10, 13q, and 20p. CDKN2A was homozygously deleted in 7/11 patients. Hypermethylation of both p16(INK4a) and p14(ARF) was found in 1/14 patients. An internal deletion of STARD13 was found in a region with common losses at 13q13.1. The most frequent gains were seen at 1q, 4q, 5p, 8q, 12p, 15q, 16q, 17q, 20q, 22q, and Xp. Single recurrent high level amplification was detected at 4q12, including KIT, PDGFRA, and KDR. No activating mutations were found in any of them. Immunohistochemistry revealed expression of PDGFRA and/or PDGFRB in 12/17 samples. Moreover, small regions of gains pinpointed genes of particular interest, such as IGF1R at 15q26.3 and CHD1L at 1q21.1. In conclusion, our analysis provided novel findings that can be exploited when searching for markers for diagnosis and prognosis, and targets of therapy in this tumor type.
Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. tarja.niini@helsinki.fi
Tarja
T
Niini
José Antonio
JA
López-Guerrero
Shinsuke
S
Ninomiya
Mohamed
M
Guled
Claudia Maria
CM
Hattinger
Francesca
F
Michelacci
Tom
T
Böhling
Antonio
A
Llombart-Bosch
Piero
P
Picci
Massimo
M
Serra
Sakari
S
Knuutila
D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2