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

Identificación de nuevas mutaciones puntuales en el gen c-kit en casos de Leucemia: un estudio realizado en Lucknow, Uttar Pradesh, India

  • Amna Siddiqui Department of Anestheology, Texas Tech University, El Paso, TX, U.S.A.
  • Syed Rizwan Hussain Department of Biochemistry, Era's Lucknow Medical College and Hospital, Lucknow, India.
  • Javier Vargas-Medrano Center of Excellence for Infectious Diseases, Biomedical Sciences Department, Texas
  • Hena Naqvi Department of Biochemistry, Era's Lucknow Medical College and Hospital, Lucknow, India.
  • Jonathon Mohl Center of Excellence for Infectious Diseases, Biomedical Sciences Department, Texas
Palabras clave: c-kit, exon-8 and -11, Leukemia, mutation, SSCP-PAGE


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 is the most frequent site 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 were detected only in three cases. These observations suggest that mutations in c-kit gene might represent a 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.


El gen c-kit, que codifica para un receptor tirosina quinasa (RTK) de clase III, se expresa en las primeras células progenitoras hematopoyéticas. La activación de este RTK y su vía de señalización se encuentran involucradas en la patogénesis molecular de varias enfermedades. La mutación del gen c-kit en el exón 11 es una de las mutaciones más frecuentemente reportadas en diferente tipos de tumores. Mutaciones en c-kit podrían incrementar o interferir con la habilidad del receptor c-kit para iniciar la activación de cascadas de señalización intracelulares responsables en la proliferación celular. Por estas razones, estudiamos las mutaciones del gen c-kit en el exon 8 y 11 en casos con Leucemias. Noventa casos de Leucemia en la India fueron estudiados mediante PCR SSCP, seguida por secuenciación de DNA. Veinte mutaciones puntuales fueron detectadas en el exon 11 en tan solo ocho de los casos con AML (leucemia mieloide aguda), entre las que encontraron las mutaciones Tyr568Ser, Ile571Thr, Thr574Pro, Gln575His, Tyr578Pro, Asp579His, His580Gln, Arg586Thr, Asn587Asp y Arg588Met. Las sustituciones Lys550Asn, Ile571Leu y Trp582Ser fueron observadas en tan solo dos casos. Además, cuatro nuevas mutaciones para los codones Ile563Lys, Val569Leu, Tyr570Ser, y Pro577Ser se observaron en este estudio. En el exon 8, seis mutaciones puntuales fueron observadas y en seis de los casos (cuatro en AML y dos en CML) encontramos tres nuevas mutaciones Asn423Asp, Gln448Thr y Gln448His. Sin embargo, las mutaciones puntuales Thr417Asp, Tyr418Phe y Leu421His fueron observadas en varias ocasiones, pero en tan solo tres de los casos estudiados. Estas observaciones sugieren que las mutaciones en c-kit podrían representar un marcador genético para Leucemia. La incidencia en la mutación del exon 8 y 11 es elevada y podría estar relacionada con la patogénesis de la AML.

Palabras clave: c-kit, exones 8 y 11, Leucemia, mutación, SSCP PAGE.


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Cómo citar
Siddiqui, A., Rizwan Hussain, S., Vargas-Medrano, J., Naqvi, H., & Mohl, J. (2020). Identification of novel point mutations in c-kit gene from Leukemia cases: a study from Lucknow, Uttar Pradesh, India: Identificación de nuevas mutaciones puntuales en el gen c-kit en casos de Leucemia: un estudio realizado en Lucknow, Uttar Pradesh, India. TECNOCIENCIA Chihuahua, 6(1), 22-32.