Amplification of chromosome 1 sequences in lipomatous tumors and other sarcomas.

Abstract

Amplifications and gains involving 1q are common abnormalities in solid tumors. Recently, an amplicon originating from 1q21-23, containing the candidate oncogenes COAS1, COAS2 and COAS3 (Chromosome One Amplified Sequence) was identified. The presence, distribution and copy number level of extra COAS sequences were investigated in 48 bone and soft tissue tumor (BSTT) samples using metaphase FISH analysis. Amplification was seen in 27/48 (56%) samples. With few exceptions, all 3 genes were involved, but on average COAS2 exhibited higher copy numbers. The presence of extra COAS signals, irrespective of copy numbers, was found at similar frequencies in different histologic tumor subtypes. However, medium or high level amplification was common in lipomatous tumors but rare in other, nonlipomatous tumors (9/21 vs. 2/27 samples). The most common localization of extra COAS signals in lipomatous tumors was in supernumerary ring and giant marker chromosomes. Among nonlipomatous tumors, the distribution of extra COAS genes was more disperse, being located in various unidentified chromosomal structures, including double minutes, and only rarely in ring chromosomes. Because MDM2 is known to be amplified frequently in BSTTs, and in particular in atypical lipomatous tumors, cases with extra copies of COAS were studied also with an MDM2 probe. Twelve out of 18 lipomatous tumors had extra copies of both COAS and MDM2, and the 2 genes were found to be coamplified and interspersed exclusively in ring and giant marker chromosomes. Also 12 out of 18 nonlipomatous tumors exhibited simultaneous gain of COAS and MDM2, but colocalization in the same chromosome was less frequent. The role of the frequent coamplification of COAS, or some other yet unknown gene in the 1q21-23 region, and MDM2 remains to be elucidated.