We are very glad to inform you that the Laboratory of Translational Cancer Genomics will collaborate with Institute of Experimental Medicine Czech Academy of Sciences and Thomayer hospital on the new project awarded by the Czech Health Research Council.
NU21-03-00145: Telomere homeostasis as potential biomarker of risk, prognosis and progression in gynaecologic tumours
Principal Investigator: MUDr. Ludmila Vodičková, CSc. (IEM CAS)
Co-investigator: Pavel Šrobánek (Thomayer Hospital)
Co-investigator: Kari Hemminki, M.D., Ph.D. (Faculty of Medicine CUNI)
Date of implementation: 1.5.2021 – 31.12.2024
Abstract:
Disruption of telomere length (TL) homeostasis in lymphocytes has been previously assessed as a potential biomarker of risk of breast (BC) and ovary (OvC) cancers. Given the fundamental role of telomerase in cancer etiology, this study aims at the determination of the telomere homeostasis dynamic in onset and progression of gynaecological cancers. The relationship of shortened telomeres in tumor tissue of aggressive BC subtypes (Luminal B, HER-2-positive and triple-negative tumors) has been previously described. In our preliminary experiment, we measured TL in lymphocytes of 611 BC patients and 154 healthy women controls: our results showed longer lymphocyte TL in the patients than in healthy subjects. It seems that TL homeostasis varies with the (sub)type of cancer. Our preliminary study on TL in BC patients has been exclusively conducted on 600 BRCA- patients. The availability of samples from families bearing BRCA mutation (BRCA+) with and without BC and BRCA- with and without BC may cast more light on telomere homeostasis in relation to this high penetrance gene in BC, which constitutes a key element in homologous recombination DNA repair. In those samples BRCA low penetrance gene variants will be assayed for. Thanks to the possession of OvC blood and tissue samples we may address the dynamic of telomere homeostasis in relation to OvC onset, prognosis and treatment. Our recent study revealed that DNA mismatch repair (MMR) emerges as an important player in telomere homeostasis and genomic stability. Since OvC has also MMR deficiency in its etiology, addressing telomere homeostasis in this context will be of outmost interest. The determination of TL should be supplemented by mRNA of telomerase genes. Regarding prognostic value of telomere homeostasis we intend to execute a follow up in 6th and 12th months from entering the study. Important information on disease prognosis and therapeutic efficacy will be acquired as well.
We are looking for this collaboration!