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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]
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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https://hal-amu.archives-ouvertes.fr/hal-01823537
Contributor : l'Houcine Ouafik Connect in order to contact the contributor
Submitted on : Tuesday, June 26, 2018 - 10:32:42 AM
Last modification on : Friday, October 22, 2021 - 3:27:02 AM

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  • HAL Id : hal-01823537, version 1
  • PUBMED : 12699056

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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, Wichtig Editore, 2003, pp.1-6. ⟨hal-01823537⟩

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