title: Chromosomal aberrations in primary PDGFRA-mutated gastrointestinal stromal tumors.
abstract: Approximately 15% of gastrointestinal stromal tumors (GISTs) harbor mutations in the platelet-derived growth factor receptor α (PDGFRA) gene. Chromosomal aberrations play a crucial role in tumor progression and correlate with clinical behavior. Imbalances, particularly in PDGFRA-mutated GISTs, have not yet been evaluated in larger series. We analyzed 53 PDGFRA-mutated GISTs (including 2 with corresponding metastases) for chromosomal imbalances by conventional comparative genomic hybridization and compared them with a historical collective of 122 KIT-mutated GISTs. PDGFRA exon 18 mutations (91% of cases) and exon 12 mutations (9% of cases) correlated significantly with gastric and intestinal sites, respectively. The most common aberrations were identical to those found in KIT-mutated GISTs, with -14q in 70%, -1p in 28%, and -22q in 17% of cases. Overall, there were significantly fewer chromosomal aberrations compared with KIT-mutated GISTs, with a mean of 2.8 (0.6 gains, 2.1 losses) aberrations per tumor. There was a statistically significant association of more than 5 chromosomal imbalances with intermediate/high-risk categories. Regarding specific chromosomal aberrations, -9p, -13q, and -22q correlated with intermediate/high risk, and -1p and +8q with poorer survival, although progression occurred in only 2 cases. Altogether, PDGFRA-mutated GISTs display the same chromosomal aberrations as KIT-mutated GISTs, although they have a lower degree of chromosomal instability in line with their generally favorable outcome.
authors.affiliation: Department of Pathology, University Medical Center Göttingen, Robert-Koch-Straße 40, Göttingen D-37075, Germany. Electronic address: inga-marie.schaefer@med.uni-goettingen.de.
authors.forename: Inga-Marie
authors.initials: IM
authors.lastname: Schaefer
authors.forename: Christian
authors.initials: C
authors.lastname: Delfs
authors.forename: Silke
authors.initials: S
authors.lastname: Cameron
authors.forename: Bastian
authors.initials: B
authors.lastname: Gunawan
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.forename: B Michael
authors.initials: BM
authors.lastname: Ghadimi
authors.forename: Florian
authors.initials: F
authors.lastname: Haller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*
chemical_list: D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: Comparative genomic hybridization; GIST; KIT; Mutation; PDGFRA