Technology in Cancer Research & Treatment (Mar 2020)

Centenarian Exomes as a Tool for Evaluating the Clinical Relevance of Germline Tumor Suppressor Mutations

  • Lubomir Balabanski MSc,
  • Dimitar Serbezov PhD,
  • Dragomira Nikolova PhD,
  • Olga Antonova PhD,
  • Desislava Nesheva PhD,
  • Zora Hammoudeh PhD,
  • Radoslava Vazharova PhD,
  • Sena Karachanak-Yankova PhD,
  • Rada Staneva PhD,
  • Marta Mihaylova PhD,
  • Vera Damyanova PhD,
  • Savina Hadjidekova PhD,
  • Draga Toncheva PhD

DOI
https://doi.org/10.1177/1533033820911082
Journal volume & issue
Vol. 19

Abstract

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Objectives: 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. Methods: 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. Results: 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 PTPRJ , rs861539 in XRCC3 , rs203462 in AKAP10 , and rs486907 in RNASEL . Discussion: 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.