Abstract |
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.
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Authors | S 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 |
Journal | The International journal of biological markers
(Int J Biol Markers)
2003 Jan-Mar
Vol. 18
Issue 1
Pg. 1-6
ISSN: 0393-6155 [Print] United States |
PMID | 12699056
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Codon
- DNA, Complementary
- Adenosine Triphosphate
- Thymidine Kinase
- thymidine kinase 1
- Cyclic AMP-Dependent Protein Kinases
- Cyclic GMP-Dependent Protein Kinases
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Topics |
- 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)
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