title: Loss of chromosome 13q is a frequently acquired event in genetic progression of soft tissue sarcomas in the abdominal cavity.
abstract: Soft tissue sarcomas (STSs) arising in the abdominal cavity constitute a group of aggressive tumours, typically of very large size and with a high recurrence rate in the affected patients. While some distinct genetic etiologies have been described, the genetic background of this tumour group is not well characterised. Here we have assessed gross chromosomal alterations in a series of such tumours obtained from 26 patients. CGH alterations were found in tumours from 23 of the patients (88%), the most frequent being loss of 13q21 (46%) and gain of 17p and/or q (46%). Furthermore, mutations of C-KIT exon 11 were demonstrated in five tumours from four patients, and the two myxoid liposarcomas exhibited a translocation t(12;16)(q13;p11). From the pattern of chromosomal alterations detected, a genetic progression of events was clearly evident in the tumours. Taken together with analysis of subsequent relapses from the same patients, the common CGH alteration +12q13 was suggested to be a relatively early event in the genetic progression, similar to t(12;16)(q13;p11) and C-KIT mutations. Moreover, -1p21-22, -13q21, -14q, -Xp22, +9q34, +17p, +17q, and +20q13 would all represent relative later events. The most consistent alteration was loss of 13q, that was found to target the 13q14-21 and 13q34 regions as determined by CGH and Southern blot analyses. Loss of 13q was identified independently of +12q13 and C-KIT mutation and the patient's sex, and was observed in all common subtypes of STS, suggesting that it is a general and late event in the genetic progression. The findings provide a starting point for further dissection of the target genes involved in development of STSs in the abdominal cavity.
authors.affiliation: Department of Molecular Medicine, CMM L8:01, Karolinska University Hospital-Solna, SE-171 76 Stockholm, Sweden. wendy.weng@cmm.ki.se
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Weng
authors.forename: Mikael
authors.initials: M
authors.lastname: Lerner
authors.forename: Dan
authors.initials: D
authors.lastname: Grandér
authors.forename: Jan
authors.initials: J
authors.lastname: Ahlén
authors.forename: Andrea
authors.initials: A
authors.lastname: Villablanca
authors.forename: See-Tong
authors.initials: ST
authors.lastname: Pang
authors.forename: Johan
authors.initials: J
authors.lastname: Wejde
authors.forename: Weng-Onn
authors.initials: WO
authors.lastname: Lui
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
mesh_terms: D000008:Abdominal Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012509:Sarcoma / Q000235:genetics*; D012737:Sex Factors; D032681:Spectral Karyotyping; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D004247:DNA; D019009:Proto-Oncogene Proteins c-kit