title: Array comparative genomic hybridization reveals distinct DNA copy number differences between gastrointestinal stromal tumors and leiomyosarcomas.
abstract: Leiomyosarcomas are spindle cell tumors showing smooth muscle differentiation. Until recently, most gastrointestinal stromal tumors (GIST) were also classified as smooth muscle tumors, but now GISTs are recognized as a separate entity, defined as spindle cell and/or epithelioid tumors localized in the gastrointestinal tract. Using microarray-based comparative genomic hybridization (array CGH), we have created a detailed map of DNA copy number changes for 7 GISTs and 12 leiomyosarcomas. Considerable gains and losses of chromosomal segments were observed in both tumor types. The most frequent aberration observed in GISTs was loss of chromosomes 14 and 22, with minimal recurrent regions in 14q11.2-q32.33 (71% of the tumors) and 22q12.2-q13.31 (100%). In leiomyosarcomas, frequent loss of chromosome 10 and 13q was observed, with minimal recurrent regions in 10q21.3 (75%) and 13q14.2-q14.3 (75%). Recurrent high-level amplification of 17p13.1-p11.2 was detected in leiomyosarcomas. Expression profiling using cDNA microarrays revealed four candidate genes in this region with high expression (AURKB, SREBF1, MFAP4, and FLJ10847). Altered expression of AURKB and SREBF1 has been observed previously in other malignancies. Hierarchical clustering of all samples separated GISTs and leiomyosarcomas into two distinct clusters. Statistical analysis identified six chromosomal regions, 1p36.11-p13.1, 9q21.11-9q34.3, 14q11.2-q23.2, 14q31.3-q32.33, 15q24.3-q26.3, and 22q11.21-q13.31, which were significantly different in copy number between GISTs and leiomyosarcomas. Our results show the potential of using array comparative genomic hybridization to classify histologically similar tumors such as GISTs and leiomyosarcomas.
authors.affiliation: Department of Tumor Biology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. leonardm@radium.uio.no
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Meza-Zepeda
authors.forename: Stine H
authors.initials: SH
authors.lastname: Kresse
authors.forename: Ana H
authors.initials: AH
authors.lastname: Barragan-Polania
authors.forename: Bodil
authors.initials: B
authors.lastname: Bjerkehagen
authors.forename: Hege O
authors.initials: HO
authors.lastname: Ohnstad
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Namløs
authors.forename: Junbai
authors.initials: J
authors.lastname: Wang
authors.forename: Bjørn E
authors.initials: BE
authors.lastname: Kristiansen
authors.forename: Ola
authors.initials: O
authors.lastname: Myklebost
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D007890:Leiomyosarcoma / Q000235:genetics*; D008297:Male; D051379:Mice; D008875:Middle Aged; D005810:Multigene Family; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014183:Transplantation, Heterologous