Experience in using high-performance parallel DNA sequencing to characterize the molecular genetic features of kidney angiomyolipoma


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Angiomyolipoma is one of the most common forms of kidney pathology in tuberous sclerosis. Since tuberous sclerosis as a genetic disorder associated with mutations in genes, TSC1 and TSC2, mutational profiling of angiomyolipoma has been limited to just these two genes. We first screened mutations by high parallel sequencing in a broad panel of genes involved in tumorigenesis in surgery samples and blood of patients with angiomyolipoma. Sequencing of the DNA of the tumor specimens revealed mutations in ЗО out of 409 examined genes. TSC2 gene mutations were identified as both of germinal and somatic nature. Apart from TSC2, the greatest number of nucleotide changes in the tumor DNA was found in ROS! gene. Noteworthy is that all the examined patients were carriers of polymorphism in the gene CYP2D6 (c.G1094A: p.R365H) which has incidence in the general population not exceeding 10%. Further search and characterization of mutations in a lager sample of patients will contribute to the study of kidney angiomyolipoma biology and provide a basis for developing new modalities to prevent and treat this disease.

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