Balabanski Lubomir, Serbezov Dimitar, Nikolova Dragomira, Antonova Olga, Nesheva Desislava, Hammoudeh Zora, Vazharova Radoslava, Karachanak-Yankova Sena, Staneva Rada, Mihaylova Marta, Damyanova Vera, Hadjidekova Savina, Toncheva Draga
Department of Medical Genetics, Medical University-Sofia, Sofia, Bulgaria.
Hospital"Malinov," Sofia, Bulgaria.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820911082. doi: 10.1177/1533033820911082.
The aim of the present study was to evaluate the clinical relevance of mutations in tumor suppressor genes using whole-exome sequencing data from centenarians and young healthy individuals.
Two pools, one of centenarians and one of young individuals, were constructed and whole-exome sequencing was performed. We examined the whole-exome sequencing data of Bulgarian individuals for carriership of tumor suppressor gene variants.
Of all variants annotated in both pools, 5080 (0.06%) are variants in tumor suppressor genes but only 46 show significant difference in allele frequencies between the two studied groups. Four variants (0.004%) are pathogenic/risk factors according to single nucleotide polymorphism database: rs1566734 in , rs861539 in , rs203462 in , and rs486907 in .
Based on their high minor allele frequencies and presence in the centenarian group, we could reclassify them from pathogenic/risk factors to benign. Our study shows that centenarian exomes can be used for re-evaluating the clinically uncertain variants.
本研究旨在利用来自百岁老人和年轻健康个体的全外显子组测序数据，评估肿瘤抑制基因突变的临床相关性。
构建了两个样本库，一个来自百岁老人，另一个来自年轻人，并进行了全外显子组测序。我们检查了保加利亚个体的全外显子组测序数据，以确定肿瘤抑制基因变体的携带情况。
在两个样本库中注释的所有变体中，5080个（0.06%）是肿瘤抑制基因中的变体，但只有46个在两个研究组之间的等位基因频率上显示出显著差异。根据单核苷酸多态性数据库，四个变体（0.004%）是致病/风险因素：位于[具体基因1]中的rs1566734、位于[具体基因2]中的rs861539、位于[具体基因3]中的rs203462以及位于[具体基因4]中的rs486907。
基于它们在百岁老人组中的高次要等位基因频率和存在情况，我们可以将它们从致病/风险因素重新分类为良性。我们的研究表明，百岁老人的外显子组可用于重新评估临床上不确定的变体。
