KIT and PDGFRA mutations in gastrointestinal stromal tumour (GIST) cases from two centres in Malaysia

Abstract

Gastrointestinal stromal tumours (GISTs) are the most common type of sarcoma in the gastrointestinal tract. The diagnosis of GIST is basically established through histopathological examination of the tumour tissues and by performing relevant immunohistochemistry staining. In addition, a mutational analysis for KIT and PDGFRA has been advocated in patients with an uncertain diagnosis or atypical morphology or clinical features in which GIST is a differential diagnosis. There is also growing evidence of phenotype-genotype and genotype-therapeutic correlations in GISTs. This study therefore aimed to detect the presence of KIT and PDGFRA mutations using a mutational analysis approach in cases diagnosed as GISTs by the conventional histopathological techniques and to examine the associations of the mutations with the pathological profiles of the cases. The formalin-fixed paraffin-embedded (FFPE) blocks and the histopathological examination reports from Hospital Tengku Ampuan Afzan and Hospital Queen Elizabeth were retrieved. Extracted DNA was subjected to DNA purification and PCR amplification for exon 11 and exon 9 of KIT gene and exon 18 of PDGFRA gene. The mutations were identified using a direct nucleotide sequencing approach. A total of 47 cases were identified. Only 21 samples were successfully amplified. KIT mutations were detected in 18 samples. The types of mutation identified were point mutation, substitution, deletion, and indel in exon 11 of KIT gene, while duplication was identified in exon 9 of KIT gene. The most frequent mutation was p.L576P point mutation in KIT exon 11, detected in 13 of 21 samples. Three samples were identified with a single nucleotide polymorphism in PDGFRA exon 18 (p.V824V). The presence of KIT mutations was significantly associated with a higher mitotic count (p=0.03). In conclusion, this study detected KIT mutations and a silent mutation in PDGFRA gene of the GIST cases studied.