Thymidine Kinase 1 in Risk Assessment for Hereditary Breast /Ovarian Cancer
Hereditary breast/ovarian cancer syndrome is associated with mutations in tumor suppressor
BRCA1 and BRCA2 genes. Products of these genes play an important role in the repair of DNA
double-strand breaks. Mutations in BRCA1 and BRCA2 genes could impair DNA repair. In resting
or G1 cells, where the de novo synthesis of DNA precursors is absent, the salvage pathway is
the sole provider of deoxyribonucleotides to be used in DNA repair. For this process a
sufficient supply of deoxynucleotides and activity of Thymidine Kinase 1 are essential. TK1
is an important component of adaptive response of cells to DNA damage. Mutations in genes
directly engaged in the DNA repair process could lead to the accumulation of DNA damage and
in turn cause an adaptive cell reaction manifesting as permanently increased Thymidine
Kinase 1 activity.
A recently developed new high-sensitive assay DiviTum® allows to investigate the
contribution of this enzyme to DNA repair processes and to make a comparison of Thymidine
kinase 1 activity in women with normal and impared DNA repair system.
Observational Model: Family-Based, Time Perspective: Prospective
Israel: Ministry of Health