title: An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies different pathways of cytogenetic evolution with prognostic implications.
abstract: To model the cytogenetic evolution in gastrointestinal stromal tumour (GIST), an oncogenetic tree model was reconstructed using comparative genomic hybridization data from 203 primary GISTs (116 gastric and 87 intestinal GISTs, including 151 newly analysed cases), with follow-up available in 173 cases (mean 40 months; maximum 133 months). The oncogenetic tree model identified three major cytogenetic pathways: one initiated by -14q, one by -1p, and another by -22q. The -14q pathway mainly characterized gastric tumours with predominantly stable karyotypes and more favourable clinical course. On the other hand, the -1p pathway was more characteristic of intestinal GISTs, with an increased capacity for cytogenetic complexity and more aggressive clinical course. Loss of 22q, more closely associated with -1p than -14q, appeared to initiate the critical transition to an unfavourable cytogenetic subpathway. This -22q pathway included accumulation of +8q, -9p, and -9q, which could all predict disease-free survival in addition to tumour site. Thus, insights into the cytogenetic evolution obtained from oncogenetic tree models may eventually help to gain a better understanding of the heterogeneous site-dependent biological behaviour of GISTs.
authors.affiliation: Institute of Pathology, Department of General Surgery, University of Göttingen, Germany, and Department of Clinical Pathology and Cytology, Merkur University Hospital, Zagreb, Croatia. bastian.gunawan@med.uni-goettingen.de
authors.forename: B
authors.initials: B
authors.lastname: Gunawan
authors.forename: A
authors.initials: A
authors.lastname: von Heydebreck
authors.forename: B
authors.initials: B
authors.lastname: Sander
authors.forename: H-J
authors.initials: HJ
authors.lastname: Schulten
authors.forename: F
authors.initials: F
authors.lastname: Haller
authors.forename: C
authors.initials: C
authors.lastname: Langer
authors.forename: T
authors.initials: T
authors.lastname: Armbrust
authors.forename: M
authors.initials: M
authors.lastname: Bollmann
authors.forename: S
authors.initials: S
authors.lastname: Gasparov
authors.forename: D
authors.initials: D
authors.lastname: Kovac
authors.forename: L
authors.initials: L
authors.lastname: Füzesi
mesh_terms: D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D020732:Cytogenetic Analysis; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics; D007621:Karyotyping; D016013:Likelihood Functions; D008957:Models, Genetic; D009362:Neoplasm Metastasis / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics; D013997:Time Factors