Elevated frequency of microsatellite mutations in TK6 human lymphoblast clones selected for mutations at the thymidine kinase locus.
Mol Cell Biol
; 14(7): 4373-9, 1994 Jul.
Article
en En
| MEDLINE
| ID: mdl-8007946
ABSTRACT
A major question in carcinogenesis is, How can a normal cell accumulate multiple mutations in different genes on different chromosomes, when the mutation rate of each gene is in the range of 10(-8) to 10(-5) per cell division? We hypothesize that many mutations may not be isolated events but rather are accompanied by concomitant mutations elsewhere in the genome. To test this hypothesis, 331 independent clones selected for new mutations at the thymidine kinase (TK) locus on chromosome 17q, and 243 nonselected control clones were examined for mutations in 12 random microsatellite loci dispersed throughout the genome. A total of 24 second-site mutations were identified in the TK mutant clones, compared with 3 in the control clones not selected for mutations at TK. The mutations include small deletions, insertions, and loss of heterozygosity. These results provide evidence that a global trans-acting mutagenic process exists in human cells. The activation of this process could be responsible for causing multiple essential mutations in tumor cells.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Timidina Quinasa
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Cromosomas Humanos Par 17
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ADN Satélite
/
Linfocitos
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Mutagénesis
Tipo de estudio:
Clinical_trials
Límite:
Humans
Idioma:
En
Año:
1994
Tipo del documento:
Article