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

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.
AuthorsS I Gilles, S Romain, P Casellas, L'H Ouafik, F Fina, T Combes, V Vuaroquaux, J F Seitz, P Bonnier, S Galiègue, P Carayon, P M Martin
JournalThe International journal of biological markers (Int J Biol Markers) 2003 Jan-Mar Vol. 18 Issue 1 Pg. 1-6 ISSN: 0393-6155 [Print] Italy
PMID12699056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Codon
  • DNA, Complementary
  • Adenosine Triphosphate
  • Thymidine Kinase
  • thymidine kinase 1
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic GMP-Dependent Protein Kinases
  • Adenosine Triphosphate (metabolism)
  • Adult
  • Aged
  • Aged, 80 and over
  • Binding Sites
  • Breast Neoplasms (genetics)
  • Cell Line, Tumor
  • Codon
  • Colorectal Neoplasms (genetics)
  • Cyclic AMP-Dependent Protein Kinases (metabolism)
  • Cyclic GMP-Dependent Protein Kinases (metabolism)
  • Cytosol (metabolism)
  • DNA Mutational Analysis
  • DNA, Complementary (metabolism)
  • Databases, Genetic
  • Humans
  • Middle Aged
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Mutation, Missense
  • Polymorphism, Genetic
  • Thymidine Kinase (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: