Publication Details (including relevant citation information):
Syed Rizwan-Hussain, Amna Siddiqui, Javier Vargas-Medrano, Hena Naqvi, Jonathon Mohl, Farzana Mahdi, and Fahim Ahmad. (2012). Identification of novel point mutations in c-kit gene from Leukemia cases: a study from Lucknow, Uttar Pradesh, India. Tecnociencia Chihuahua. 6(1):22-32.
The c-Kit gene is a receptor tyrosine kinase (RTK) class III that is expressed in early hematopoietic progenitor cells. Aberrantly activated RTK and related downstream signaling partners have been reported as key elements in the molecular pathogenesis of several malignancies. Within the c-kit gene exon-11 are the most frequent sites for mutations in different kinds of tumours. Mutations in c-kit gene may enhance or interfere with the ability of c-kit receptor to initiate the intracellular pathways resulting in cell proliferation. Therefore, we aimed to screen the mutations in c-kit gene at exon-8 and -11 in malignant Leukemias. Ninety Leukemia cases were studied and analyzed by mutation-specific PCR-SSCP followed by DNA sequencing. Twenty point mutations were detected in eight AML (acute myeloid Leukemia) cases within exon-11 which includes Tyr568Ser, Ile571Thr, Thr574Pro, Gln575His, Tyr578Pro, Asp579His, His580Gln, Arg586Thr, Asn587Asp and Arg588Met. The substitutions Lys550Asn, Ile571Leu and Trp582Ser were observed in two independent cases and four novel point mutations at codons Ile563Lys, Val569Leu, Tyr570Ser, and Pro577Ser. Further, six point mutations were detected at exon-8 in six cases (four AML and two CML cases), comprising three novel mutations Asn423Asp, Gln448Thr and Gln448His. The point mutations Thr417Asp, Tyr418Phe and Leu421His were observed but was detected only in three cases. These observations suggest that mutations in c-kit gene might represent useful molecular genetic marker in Leukemia and incidence of mutation at exon-8 and -11 is high and might be involve in pathogenesis of AML.