Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer.

S Gilles (1) , S. Romain (1) , P. Casellas (1) , L'H Ouafik (1) , F. Fina (1) , T Combes (1) , V Vuaroquaux (1) , S Seitz (1) , P. Bonnier (1) , S Galiègue (1) , P. Carayon (1) , P. Martin (1)

1 Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM]

We report the first mutational study of thymidine kinase 1 (TK1) performed in human solid tumors. We sequenced cDNAs representing the complete coding region of TK1 in human breast (n=22) and colorectal (n=26) cancer. Codon 106 near the ATP binding site constantly differed (ATG --> GTG; Met --> Val) from the one deposited by Bradshaw and Deininger in the Genbank database (Accession number NM_003258). Silent polymorphisms at codon 11 (CCC --> CCT; Pro --> Pro) and codon 75 (GCG --> GCA; Ala --> Ala) were frequently detected in tumors as well as in normal tissues. In breast cancer the two polymorphisms were observed in 63.6% of the samples analyzed. No significant association could be found between polymorphisms and TK activity. In colorectal cancer the incidence of the two changes was 73.1% and 69.2%, respectively. Interestingly, one colon cancer with high cytosolic TK activity displayed two missense mutations located in and near the putative phosphorylation site by tyrosine kinase (s) (TAT --> CAT; Tyr --> His) and by cAMP-, cGMP-dependent protein kinase (TAC --> TGC; Tyr --> Cys), respectively; adjacent normal mucosa showed no mutation. This may open new avenues that imply TK1 activity in tumor cell proliferation.

Domains: Life Sciences [q-bio]; Cancer

S Gilles, S. Romain, P. Casellas, L'H Ouafik, F. Fina, et al.. Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer.. international Journal of Biological Markers, 2003, pp.1-6. ⟨hal-01823537⟩