Germline and Somatic Mutations of Genes Involved in Tumor Formation in Sporadic Renal Angiomyolipoma

Resumo

Angiomyolipoma (AML) is one of the most frequent and, at the same time, AML molecular genetics is one of the least studied among benign tumors. We performed deep sequencing of 409 genes involved in oncogenesis in tumor samples and peripheral blood of patients with sporadic AML of the kidney. We recorded mutations in the TSC2 gene in 65% of samples, which is consistent with international results. As a result of our work, we uncovered mutations in the SETD2, PDGFRA, STK36, SYNE1, PIK3CD, NF1, TOP1, and ITGB3 genes in sporadic renal AML for the first time. In two samples, we were able to clarify the clinical and morphological diagnosis by finding mutations in the genes in tumors lacking TSC2 gene lesions. Mutations in MET and CDC73 are also causative for other types of renal tumors: papillary renal cell carcinoma and CDC73-related disorders, respectively. The latter disease is accompanied by kidney cysts and hamartomas. The obtained results demonstrate a promising potential of mutational profiling of sporadic renal angiomyolipoma (sAML). Genotyping of sAML is particularly important for clarification of the clinical diagnosis in ambiguous cases, as well as for a more in-depth understanding of AML molecular genetics and etiopathogenesis, and for the identification of new molecular targets for personalized AML therapies.