Detection of NRAS G12D and NRAS G13C mutant genes among apparently healthy and haematologic malignant individuals in Federal Capital Territory, Nigeria

Abstract

ABSTRACT Rat Sarcoma gene mutations is an important aspect in the management of hematologic malignancies globally. Unfortunately, this is not the trend in West Africa, including Nigeria. This study was aimed at detecting NRAS G12D and NRAS G13C mutant genes among apparently healthy and haematologic malignant individuals, and to explore their association with some clinical and demographic factors as well as disease status and progression. A total of 200 cfDNAs, 100 each from haematologic malignant patients and blood donors, respectively, were analyzed for the presence of NRAS gene mutations in codons 12 and 13. These mutations were tested using multiplex allele-specific PCR (AS-PCR). The mutations were detected by selective amplification using mutation-specific synthetic oligonucleotides. NRAS G12D and NRAS G13C mutations were 20.0% and 10.0%, respectively. In 17.5% of the 100 haemapoietic cancer patients, NRAS G12D mutant genes were seen while 7.5% of NRAS G13C mutation was found. Both mutant genes were observed in five healthy blood donors each. This result confirms the existence of NRAS mutations in Nigerian haemapoietic cancer patients and the preponderance of G-A transitions over G-T transversions. Mutant NRAS genes were associated with the types and stages of cancer, highlighting probable connection between mutation and increased susceptibility as well as quick progression of hematologic malignancies in the population studied. The result also highlighted higher risk of susceptibility/progression associated with leukemia than other hematopoietic cancers. We recommend more studies on NRAS mutation specifically targeted at improved diagnosis and prognostic therapy. The role of RAS mutation should be explored in other aside blood cancers in the Nigerian population.