title: Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma.
abstract: To search for new recurrent genetic aberrations in malignant fibrous histiocytoma (MFH), a combination of conventional cytogenetic, comparative genomic hybridization (CGH), and Southern blot analyses was applied to a series of 34 tumors. Cytogenetic 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) (CDKN2A; 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 frequent loss and amplification, respectively. These data indicate that genes involved in the RB1- and TP53-associated cell cycle regulatory pathways may play prominent roles in the development of human MFH.
authors.affiliation: Department of Human Genetics, University Hospital, Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Simons
authors.forename: M
authors.initials: M
authors.lastname: Schepens
authors.forename: J
authors.initials: J
authors.lastname: Jeuken
authors.forename: S
authors.initials: S
authors.lastname: Sprenger
authors.forename: G
authors.initials: G
authors.lastname: van de Zande
authors.forename: B
authors.initials: B
authors.lastname: Bjerkehagen
authors.forename: A
authors.initials: A
authors.lastname: Forus
authors.forename: V
authors.initials: V
authors.lastname: Weibolt
authors.forename: I
authors.initials: I
authors.lastname: Molenaar
authors.forename: E
authors.initials: E
authors.lastname: van den Berg
authors.forename: O
authors.initials: O
authors.lastname: Myklebost
authors.forename: J
authors.initials: J
authors.lastname: Bridge
authors.forename: A G
authors.initials: AG
authors.lastname: van Kessel
authors.forename: R
authors.initials: R
authors.lastname: Suijkerbuijk
mesh_terms: D015139:Blotting, Southern; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D003720:Densitometry; D005260:Female; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D008297:Male; D009693:Nucleic Acid Hybridization; D012983:Soft Tissue Neoplasms / Q000235:genetics*