Frequent amplification and rearrangement of chromosomal bands 6p12‐p21 and 17p11.2 in osteosarcoma

TLDR

Osteosarcoma is a highly malignant bone tumor in children and young adults, characterized by chaotic karyotypes with complex marker chromosomes. The study used comparative genomic hybridization, spectral karyotyping, and fluorescence in situ hybridization—including BAC clone probes—to analyze chromosomal complexity and identify genes within 6p and 17p amplicons in 25 tumors. Analysis revealed novel recurrent breakpoint clusters, nine nonrecurrent translocations, multiple chromosomal losses and gains, and frequent high‑level amplifications at 6p12‑p21 and 17p11.2 in 28% and 32% of cases, respectively. © 2004 Wiley‑Liss, Inc.

Abstract

Abstract 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. © 2004 Wiley‐Liss, Inc.