Mutations in two neuroblastoma rat sarcoma oncogenes are associated with progression of haematologic malignancies in Nigeria

Abstract

Although mutation in the RAS genes has become important in the evaluation of haematologic malignancies worldwide, developing countries like Nigeria are yet to integrate it as a diagnostic tool and prognostic indicator for improved therapy. This study determined mutations in codons 12 and 13 of NRAS gene in blood donors and haematologic malignant individuals using multiplex (AS-PCR) and Sanger sequencing, thus highlighting the mutations as helpful diagnostic and prognostic tool. AS-PCR was used to selectively amplify mutation-specific synthetic oligonucleotides from the cfDNA of 100 study participants (50 cancer patients and 50 blood donors). Percentage mutation of 31.0% was seen in NRAS_G12D gene while NRAS_G13C had 17.0%. Twenty nine (29.0%) of the NRAS_G12D mutations were found in haematopoietic malignant patients and 2.0% were found in blood donors, while 15.0% of the NRAS_G13C were found in the malignant patients, confirming the occurrence of NRAS gene mutations in haematologic cancers and predominance of the G-A transition. The highest rate of mutation was observed in leukaemia patients, having a significant association with codon 13 (p = 0.042). Stages 3 and 2 cancers each had the highest mutation rates of NRAS_G12D and NRAS_G13C, revealing possible link between these mutations and susceptibility and progression of haematologic malignancies, which is higher in leukaemia. Further NRAS mutation studies and its role in other cancers are advocated, especially targeted towards ameliorating diagnosis and prognostic therapy. Challenges related to diagnosis and management of haematologic cancer continue to persist in developing countries like Nigeria. Thus, there is a need to go beyond studying the incidence and distribution pattern of these malignancies to capturing immunogenetic parameters of affected individuals.