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.
Gilles
S I
SI
Laboratoire de Transfert d'Oncologie Biologique, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
Romain
S
S
Casellas
P
P
Ouafik
L'H
L
Fina
F
F
Combes
T
T
Vuaroquaux
V
V
Seitz
J F
JF
Bonnier
P
P
Galiègue
S
S
Carayon
P
P
Martin
P M
PM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D030541:Databases, Genetic; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D013937:Thymidine Kinase / Q000235:genetics*
D003062:Codon; D018076:DNA, Complementary; D000255:Adenosine Triphosphate; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases