Molecular characterisation of gastrointestinal stromal tumours in a South African population

dc.contributor.authorBaker, Gillian
dc.contributor.authorBabb, Chantal
dc.contributor.authorSchnugh, Desmond
dc.contributor.authorNayler, Simon
dc.contributor.authorMelanie, Louw
dc.contributor.authorGoedhals, Jacqueline
dc.contributor.authorBringuier, Pierre-Paul
dc.contributor.authorBlay, Jean-Yves
dc.contributor.authorWillem, Pascale
dc.date.accessioned2013-12-09T07:32:56Z
dc.date.available2014-06-30T00:20:05Z
dc.date.issued2013
dc.description.abstractGastrointestinal 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.en_US
dc.description.librarianam2013en_US
dc.description.urihttp://www.spandidos-publications.com/ol/en_US
dc.identifier.citationBaker, G, Babb, C, Schnugh, D, Nayler, S, Louw, M, Goedhals, J, Bringuier, PP, Blay, JY & Willem, P 2013, 'Molecular characterisation of gastrointestinal stromal tumours in a South African population', Oncology Letters, vol. 5, no. 1, pp. 155-166.en_US
dc.identifier.issn1792-1074 (print)
dc.identifier.issn1792-1082 (online)
dc.identifier.other10.3892/ol.2012.1013
dc.identifier.urihttp://hdl.handle.net/2263/32725
dc.language.isoenen_US
dc.publisherSpandisosen_US
dc.rights© 2013 Spandidos Publications Ltd. All rights reserveden_US
dc.subjectGastrointestinal stromal tumoursen_US
dc.subjectKIT mutationsen_US
dc.subjectPDGFRα mutationsen_US
dc.subjectSouth Africaen_US
dc.titleMolecular characterisation of gastrointestinal stromal tumours in a South African populationen_US
dc.typeArticleen_US

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