Molecular analysis of mutations in mutator colorectal carcinoma cell lines.
Hum Mol Genet
; 4(11): 2057-64, 1995 Nov.
Article
em En
| MEDLINE
| ID: mdl-8589681
ABSTRACT
The nature of mutations occurring in two colorectal carcinoma cell lines deficient in mismatch repair and displaying mutator phenotypes was determined. One of the lines (HCT116) exhibited a higher level of microsatellite instability than the second (DLD-1), although the rate of mutation at the selectable locus encoding the purine salvage enzyme hypoxanthine guanine phosphoribosyl transferase (HPRT) was equally elevated (about 350-450-fold relative to mismatch repair proficient cell lines). Transitions were the major class of mutations in the two mutator lines. In DLD-1 these mutations recurred at several sites that appeared to be hotspots. Frameshifts at a run of six guanine residues in the coding sequence for HPRT constituted 35% of mutations in HCT116. These frameshifts were highly unstable and reverted to wild type at high frequency. Larger deletions were also detected in HCT116. Although these deletions constituted a small proportion of mutations compared with the other types, our data suggest that the rate of deletion is elevated relative to mismatch repair proficient (hMLH1+) cell lines. These observations suggest that the gene(s) altered in DLD-1 may preferentially affect the repair of base mismatches while the alteration(s) in HCT116 may affect the repair of both mismatches and frameshifts.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Hipoxantina Fosforribosiltransferase
/
Mutação
Idioma:
En
Ano de publicação:
1995
Tipo de documento:
Article