Zdeněk Kleibl

Laboratory of oncogenetics

Cancer in genes and genes in cancer.

  • Mission: Mapping cancer predisposition in the Czech Republic.
  • Vision: Reduction of cancer incidence in the Czech Republic by persons with genetic predisposition.

Hereditary tumors represent a specific subset of cancer diagnoses characterized by the presence of a germline genetic alteration affecting some of the hundreds of cancer predisposition genes that have been characterized. Carriers of pathogenic variants in these genes are at significantly increased risk of developing cancer, and their tumors, which may develop at a significantly younger age than their sporadic counterparts, may have unique clinical features caused by different biological behaviors.

SELECTED PUBLICATIONS
  • Hovhannisyan M, Zemankova P, Nehasil P, Matejkova K, Borecka M, Cerna M, Dolezalova T, Dvorakova L, Foretova L, Horackova K, Jelinkova S, Just P, Kalousova M, Kral J, Machackova E, Nemcova B, Safarikova M, Springer D, Stastna B, Tavandzis S, Vocka M, Zima T, Soukupova J, Kleiblova P, Ernst C, Kleibl Z, Janatova M. Population-specific validation and comparison of the performance of 77- and 313-variant polygenic risk scores for breast cancer risk prediction. Cancer. 2024 May 8. DOI: 10.1002/cncr.35337
  • Stolarova L, Kleiblova P, Zemankova P, Stastna B, Janatova M, Soukupova J, …, Macurek L, Kleibl Z. ENIGMA CHEK2gether project: a comprehensive study identifies functionally-impaired CHEK2 germline missense variants associated with increased breast cancer risk. Clin Cancer Res. 2023;29(16):3037-3050. DOI: 10.1158/1078-0432.CCR-23-0212
  • Yang X, Leslie G, Doroszuk A, …, Kleibl Z, Kleiblova P, … Soukupova J, …Janatova M,…Tischkowitz M. Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families. J Clin Oncol. 2020;38(7):674-685. DOI: 10.1200/JCO.19.01907
  • Kleiblova P, Stolarova L, Krizova K, Lhota F, Hojny J, Zemankova P, Havranek O, Vocka M, Cerna M, Lhotova K, Borecka M, Janatova M, Soukupova J, Sevcik J, Zimovjanova M, Kotlas J, Panczak A, Vesela K, Cervenkova J, Schneiderova M, Burocziova M, Burdova K, Stranecky V, Foretova L, Machackova E, Tavanzis S, Kmoch S, Macurek L, Kleibl Z. Identification of deleterious germline CHEK2 mutations and their association with breast and ovarian cancer. Int J Cancer. 2019;145(7):1782-1797. DOI: 10.1002/ijc.32385
  • Meulendijks D, Henricks LM, Sonke GS, Deenen MJ, Froehlich TK, Amstutz U, Largiadèr CR, Jennings BA, Marinaki AM, Sanderson JD, Kleibl Z, Kleiblova P, Schwab M, Zanger UM, Palles C, Tomlinson I, Gross E, van Kuilenburg AB, Punt CJ, Koopman M, Beijnen JH, Cats A, Schellens JH. Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data. Lancet Oncol. 2015;16(16):1639-50. DOI: 10.1016/S1470-2045(15)00286-7
SPECIALIZED EXPERTISE AND TECHNOLOGY

Germline genetic testing

Variant classification

Functional analyses

RNA/splicing analyses

Pharmacogenomics

COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES

Czech National Infrastructure for Biological Data ELIXIR CZ

Biotechnology and Biomedicine Centre of the Czech Academy of Sciences and the Charles University BIOCEV

Masaryk Memorial Cancer Institute MMCI

Central European Institute of Technology at Masaryk University CEITEC MU