Novel chromosomal regions with loss of heterozygosity in sporadic angiomyolipoma of the kidney

Sporadic angiomyolipoma of the kidney is the most common type of renal benign tumors with an estimated frequency of 1 case per 250 people. Despite the asymptomatic course, with the increase of the tumor size, the risk of rupture of micro- and macroaneurysms also increases, which threatens the patient’s life. The use of mTOR protein kinase inhibitors leads to tumor reduction. However, such drugs are prescribed only if the patient has a somatic or germline mutation in the TSC1 or TSC2 genes the products of which are endogenous mTOR inhibitors in the reaction cascade of the PI3K/Akt/mTOR pathway. According to the COSMIC database, driver mutations in the TSC1 and TSC2 genes were identified only in 57% of angiomyolipoma cases, whereas the causes of the remaining cases are still not clear. We have conducted a loss of heterozygosity (LOH) screening in 20 sporadic kidney AML samples by use of the NGS. In seven of the twenty samples, LOH was found in different chromosome regions. In five samples, LOH encompasses the 16p13.3 region, where the TSC2 gene is located. In two samples with the normal allelic state of the 16p13.3 region, we have detected alternative LOH events encompassing 15q14q15.1 in one case, and multiple chromosomal regions in another (high chromosomal instability).

ангиомиолипома, потеря гетерозиготности, высокопроизводительное параллельное секвенирование ДНК, хромосомный микроматричный анализ. Авторы декларируют отсутствие конфликта интересов, angiomyolipoma, loss of heterozygosity, NGS, Chromosomal Microarray Analysis

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