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Article

Molecular characterisation of gastrointestinal stromal tumours in a South African population

  • Authors:
    • Gillian Baker
    • Chantal Babb
    • Desmond Schnugh
    • Simon Nayler
    • Melanie Louw
    • Jacqueline Goedhals
    • Pierre-Paul Bringuier
    • Jean-Yves Blay
    • Pascale Willem
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Medicine and Haematology, Faculty of Health Sciences, National Health Laboratory Services and University of the Witwatersrand, Johannesburg, Republic of South Africa, National Cancer Registry and Research, NHLS/MRC Cancer Epidemiology Research Group, National Health Laboratory Services, Johannesburg, Republic of South Africa , Department of Molecular Medicine and Haematology, Faculty of Health Sciences, National Health Laboratory Services and University of the Witwatersrand, Johannesburg, Republic of South Africa, Department of Histopathology, Partner Drs Gritzman and Thatcher, The Wits University Donald Gordon Medical Centre, Johannesburg, Republic of South Africa, Department of Anatomical Pathology, National Health Laboratory Service and University of Pretoria, Tshwane, Republic of South Africa, Department of Anatomical Pathology, Faculty of Health Sciences, National Health Laboratory Service and University of the Free State, Bloemfontein, Republic of South Africa, Department of Pathology, Edouard Herriot Hospital and University of Lyon, Lyon, France, Department of Medical Oncology, Center Leon Berard, University Claude Bernard, Lyon, France
  • Pages: 155-160
    |
    Published online on: November 5, 2012
       https://doi.org/10.3892/ol.2012.1013
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Baker G, Babb C, Schnugh D, Nayler S, Louw M, Goedhals J, Bringuier P, Blay J and Willem P: Molecular characterisation of gastrointestinal stromal tumours in a South African population. Oncol Lett 5: 155-160, 2013.
APA
Baker, G., Babb, C., Schnugh, D., Nayler, S., Louw, M., Goedhals, J. ... Willem, P. (2013). Molecular characterisation of gastrointestinal stromal tumours in a South African population. Oncology Letters, 5, 155-160. https://doi.org/10.3892/ol.2012.1013
MLA
Baker, G., Babb, C., Schnugh, D., Nayler, S., Louw, M., Goedhals, J., Bringuier, P., Blay, J., Willem, P."Molecular characterisation of gastrointestinal stromal tumours in a South African population". Oncology Letters 5.1 (2013): 155-160.
Chicago
Baker, G., Babb, C., Schnugh, D., Nayler, S., Louw, M., Goedhals, J., Bringuier, P., Blay, J., Willem, P."Molecular characterisation of gastrointestinal stromal tumours in a South African population". Oncology Letters 5, no. 1 (2013): 155-160. https://doi.org/10.3892/ol.2012.1013
Copy and paste a formatted citation
x
Spandidos Publications style
Baker G, Babb C, Schnugh D, Nayler S, Louw M, Goedhals J, Bringuier P, Blay J and Willem P: Molecular characterisation of gastrointestinal stromal tumours in a South African population. Oncol Lett 5: 155-160, 2013.
APA
Baker, G., Babb, C., Schnugh, D., Nayler, S., Louw, M., Goedhals, J. ... Willem, P. (2013). Molecular characterisation of gastrointestinal stromal tumours in a South African population. Oncology Letters, 5, 155-160. https://doi.org/10.3892/ol.2012.1013
MLA
Baker, G., Babb, C., Schnugh, D., Nayler, S., Louw, M., Goedhals, J., Bringuier, P., Blay, J., Willem, P."Molecular characterisation of gastrointestinal stromal tumours in a South African population". Oncology Letters 5.1 (2013): 155-160.
Chicago
Baker, G., Babb, C., Schnugh, D., Nayler, S., Louw, M., Goedhals, J., Bringuier, P., Blay, J., Willem, P."Molecular characterisation of gastrointestinal stromal tumours in a South African population". Oncology Letters 5, no. 1 (2013): 155-160. https://doi.org/10.3892/ol.2012.1013
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