Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma

To search new recurrent genetic aberrations in malignant fibrous histiocyto ma (MFH), a combination of cytogenetic, comparative genomic hybridization ( CGH), and Southern blot analyses was applied to a series of 34 tumors. Cyto genetic analysis revealed the presence of multiple structural and numerical aberrations, including marker chromosomes, telomeric associations, double minutes, and ring chromosomes. The most frequent genomic imbalances in this series of neoplasms as detected by CGH were gains of 1q21-q22 (69%), 17q23 -qter (41%), and 20q (66%), and losses of 9p21-pter (55%), 10q (48%), 11q23 -qter (55%), and 13q10-q31 (55%). Southern blot analyses with p16(INK4A) (C DKN2A; 9p21) and RB1 (13q14) probes provided clear indications for frequent deletions of these tumor suppressor genes, and as such, substantiated the CGH results. Additionally, examination of the TP53 and MDM2 genes showed fr equent loss and amplification, respectively. These data indicate that genes involved in the RB1- and TP53-associated cell cycle regulatory pathways ma y ploy prominent roles in the development of human MFN. (C) Elsevier Scienc e Inc., 2000. All rights reserved.