title: Site-independent prognostic value of chromosome 9q loss in primary gastrointestinal stromal tumours.
abstract: Although the significance of tumour site for estimating malignant potential in gastrointestinal stromal tumours (GISTs) has recently been recognized, site-specific genetic patterns have not to date been defined. This study examined 52 c-kit-positive primary GISTs (with a mean follow-up of 42.3 months in 51 cases) from three different locations (35 gastric, 12 small intestinal, and five colorectal) using comparative genomic hybridization (CGH). In general, tumour site correlated with key prognostic factors, including tumour size, mitotic rate, proliferative activity, and probable malignant potential. Furthermore, several DNA copy number changes showed a site-dependent pattern. These included losses at 14q (gastric 83%, intestinal 35%; p = 0.001), losses at 22q (gastric 46%, intestinal 82%; p = 0.02), losses at 1p (gastric 23%, intestinal 88%; p = 1 x 10(-5)), losses at 15q (gastric 14%, intestinal 59%; p = 0.002), losses at 9q (gastric 14%, intestinal 53%; p = 0.006), and gains at 5p (gastric 11%, intestinal 53%; p = 0.002). These data demonstrate strong site-dependent genetic heterogeneity in GISTs that may form a basis for subclassification. Prognostic evaluation of DNA copy number changes identified losses at 9q as a site-independent prognostic marker associated with shorter disease-free survival (p = 0.03) and overall survival (p = 0.002). Furthermore, 9q loss also appeared to carry prognostic value in predicting overall survival for patients with advanced or progressive GISTs (p = 0.003).
authors.affiliation: Institute of Pathology, University of Goettingen, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Gunawan
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Schulten
authors.forename: Anja
authors.initials: A
authors.lastname: von Heydebreck
authors.forename: Bettina
authors.initials: B
authors.lastname: Schmidt
authors.forename: Christina
authors.initials: C
authors.lastname: Enders
authors.forename: Jörg
authors.initials: J
authors.lastname: Höer
authors.forename: Claus
authors.initials: C
authors.lastname: Langer
authors.forename: Phillip
authors.initials: P
authors.lastname: Schüler
authors.forename: Christian G
authors.initials: CG
authors.lastname: Schindler
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhlgatz
authors.forename: László
authors.initials: L
authors.lastname: Füzesi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology; D007621:Karyotyping; D008297:Male; D008637:Mesenchymoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm