Frequent amplification and rearrangement of chromosomal bands 6p12-p21 and 17p11.2 in osteosarcoma.
Osteosarcoma (OS) is a highly malignant bone neoplasm of children and young adults. It is characterized by chaotic karyotypes with complex marker chromosomes. We applied a combination of molecular cytogenetic techniques including comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH) to decipher the chromosomal complexity in a panel of 25 tumors. Combined SKY and G-banding analysis identified several novel recurrent breakpoint clusters and 9 nonrecurrent reciprocal translocations. CGH identified several recurrent chromosomal losses including 2q, 3p, 9, 10p, 12q, 13q, 14q, 15q, 16, 17p, and 18q, gains including Xp, Xq, 5q, 6p, 8q, 17p, and 20q, and high-level chromosomal amplifications at Xp11.2, 1q21-q22, 4p11, 4q12, 5p15, 6p12.1, 8q13, 8q23, 10q11, 10q22, 11q13, 11q23, 12q13-q14, 13q21-q34, 16q22, 17p11.2, 17q21-q22, 18q22, 20p11.2, and 20q12. Frequent amplification and rearrangement involving chromosomal bands at 6p12-p21 and 17p11.2 were found in 28% and 32% of cases, respectively. In an attempt to identify the genes involved in these amplicons, we used three nonoverlapping BAC clones contained within each amplicon as probes for FISH analysis, leading to a more detailed characterization and quantification of the 6p and 17p amplicons.
Lau
Ching C
CC
Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA. clau@txccc.org
Harris
Charles P
CP
Lu
Xin-Yan
XY
Perlaky
Laszlo
L
Gogineni
Sheila
S
Chintagumpala
Murali
M
Hicks
John
J
Johnson
Mark E
ME
Davino
Nelson A
NA
Huvos
Andrew G
AG
Meyers
Paul A
PA
Healy
John H
JH
Gorlick
Richard
R
Rao
Pulivarthi H
PH
D000293:Adolescent; D002648:Child; D002871:Chromosome Banding; D019457:Chromosome Breakage / Q000235:genetics; D020223:Chromosome Painting; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping / Q000379:methods; D008297:Male; D009693:Nucleic Acid Hybridization; D012516:Osteosarcoma / Q000235:genetics*