title: Molecular characterisation of gastrointestinal stromal tumours in a South African population.
abstract: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. Pathogenesis is linked to activating mutations identified in two proto-oncogenes, v-kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homologue KIT (KIT) and the platelet-derived growth factor α (PDGFRα). In addition, these mutations affect response to treatment with tyrosine kinase inhibitors. In the present study, we report on the molecular characterisation of GISTs in the South African population. Tumour DNA was extracted from 46 GIST samples, followed by cycle sequencing of KIT exons 11, 13 and 17 and PDGFRα exons 12, 14 and 18. Fragment length analysis was used to detect a 6-bp duplication in KIT exon 9. Wild-type duplications were analysed further by PCR and sequencing of additional KIT and PDGFRα exons was performed. Overall, 78.3% of the samples had a mutation in KIT or PDGFRα. Of these, mutations were detected in KIT exon 11 (88.9%), PDGFRα exon 18 (8.3%) and KIT exon 9 (2.8%). Mutations varied from simple substitutions and duplications to large deletions (some with nucleotide insertions) resulting in missense mutations. In addition, seven single nucleotide polymorphisms were detected in 17 patients, one of which appears novel. The incidence of mutations in KIT exon 11 and PDGFRα exon 18 is consistent with the literature, however, the low incidence of KIT exon 9 mutations detected was unexpected. In contrast to previous western and Asian studies, this mutation appears to be rare in the South African population. The present study contributes to the molecular understanding of GISTs in the South African population.
authors.affiliation: Department of Molecular Medicine and Haematology, Faculty of Health Sciences, National Health Laboratory Services and University of the Witwatersrand;
authors.forename: Gillian
authors.initials: G
authors.lastname: Baker
authors.forename: Chantal
authors.initials: C
authors.lastname: Babb
authors.forename: Desmond
authors.initials: D
authors.lastname: Schnugh
authors.forename: Simon
authors.initials: S
authors.lastname: Nayler
authors.forename: Melanie
authors.initials: M
authors.lastname: Louw
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Goedhals
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Bringuier
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Pascale
authors.initials: P
authors.lastname: Willem