Javier Vargas Medrano - Identification of novel point mutations in c-kit gene from Leukemia cases: a study from Lucknow, Uttar Pradesh, India

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    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.

  Address (URL): http://tecnociencia.uach.mx/numeros/v6n1/data/Identification_of_novel_point_muta tions_in_c-kit_gene_from_Leukemia_cases_a_study_from_Lucknow_Uttar_Pradesh_Indi a .pdf