Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-6-25
pubmed:abstractText
The initiating mutations of a tumor are present in each of the cancerous cells comprising the tumor. Identification and measurement of the subsequent mutations that occur during tumor progression, however, requires mutation detection in a smaller subset of the tumor cells. In this study, allele-specific competitive blocker PCR (ACB-PCR), a genotypic selection method with the sensitivity to detect a specific point mutation in the presence of a 10(5)-fold excess of wild-type DNA sequence, was used to measure H-ras codon 61 CAA to AAA mutation in mouse liver tumors that did not have this mutation as an initiating event. Twenty-one spontaneous or chemically induced mouse liver tumors, negative for the H-ras codon 61 CAA to AAA mutation by DNA sequencing or denaturing gradient gel electrophoresis, were analyzed for this mutation by ACB-PCR. The mutation was detected at some level in 71% of these tumors. The mutation was detected in adenomas and carcinomas more frequently (13 of 14 tumors) and at significantly higher mutant fractions than it was detected in histiocytic sarcomas (1 of 5 tumors). These data indicate that the same oncogenic point mutation that can be identified as a tumor-initiating event based on its clonal amplification in a tumor can also be present in only a small sub-population of tumor cells where the mutation must have been fixed at a later stage in tumor development. The occurrence of a mutation as a primary or secondary event probably reflects the stochastic nature of mutation and is likely to be affected by the mutation rate for each target site.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
943-8
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Occurrence of H-ras codon 61 CAA to AAA mutation during mouse liver tumor progression.
pubmed:affiliation
Division of Genetic and Reproductive Toxicology and Division of Biochemical Toxicology, HFT-120, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA. bparsons@nctr.fda.gov
pubmed:publicationType
Journal Article