Introduction:
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. Mutational analysis for KIT and PDGFRA genes is currently a standard practice to confirm the diagnosis of GIST, and to predict sensitivity to molecular targeted therapy. Centralization of mutational analysis in a laboratory enrolled in an external quality assurance program and with expertise in the disease is recommended. In the present study, we report our local experience to implement a standard gene analysis procedure for successful GIST mutation analysis and provide the preliminary results on the molecular characterization of GISTs in Moroccan population
Methods:
Formalin-fixed paraffin-embedded (FFPE) GIST samples were used. Slide from each block was reviewed by experienced pathologists and the tumour area selected for DNA extraction
DNA was extracted from tumor areas containing at least 80% of tumor cells. Mutation of KIT exons 9, 11, 13 and 17 and PDGFRA exons 12, 14 and 18 were identified by Sanger sequencing of PCR products. Mutation nomenclature followed the recommendations of the Human Genome Variation Society (www.hgvs.org). Protocols and results were reviewed and validated in an international reference center [Institut Bergonié, Bordeaux, France]
Results: 47 GISTs were analyzed for Kit Exon 11. Mutations were found in 23 cases (48, 9%); mainly deletions, followed by substitutions, and nucleotide insertions. Cases without mutations within exon 11 of Kit were analyzed for Kit exon 9 and PDGFRA exon 18; mutations were found in 3 cases and in 1 case respectively. Mutations localized within exon 9 were duplications. Further mutational analysis of KIT exon 13; 17 and PDGFRA exon 12; 14 will be investigated and reported. Single nucleotide polymorphisms (SNPs) in PDGFRA exon 18 (c.2472 C > T p.val 824 val) were detected in 3 cases
Conclusion: The genetic profile of Moroccan GIST patients is currently unknown and further investigation is required in this area of research. The present study is likely to contribute to the characterization of the molecular profile of GIST in Morocco