Analysis of MSH3 in endometrial cancers with defective DNA mismatch repair.
J Soc Gynecol Investig
; 5(4): 210-6, 1998.
Article
em En
| MEDLINE
| ID: mdl-9699180
ABSTRACT
OBJECTIVE:
To clarify the origin of defective mismatch repair (MMR) in sporadic endometrial cancers with microsatellite instability (MSI), a thorough mutation analysis was performed on the human mismatch repair gene MSH3.METHODS:
Twenty-eight MSI-positive endometrial cancers were investigated for mutations in the human mismatch repair gene MSH3 using single-strand conformation variant (SSCV) analysis of all 24 exons. All variants were sequenced. Loss of heterozygosity was investigated at all MSH3 polymorphisms discovered. A subset of tumors were investigated for methylation of the 5' promoter region of MSH3 using Southern blot hybridization.RESULTS:
An identical single-base deletion (delta A) predicted to result in a truncated proteins was discovered in six tumors (21.4%). This deletion occurs in a string of eight consecutive adenosine residues (A8). Because simple repeat sequences are unstable in cells with defective MMR, the observed mutation may be an effect, rather than a cause, of MSI. Evidence of inactivation of the second MSH3 allele in tumors with the delta A mutation would strongly support a causal role for these MSH3 mutations. However, there was no evidence of a second mutation, loss of sequences, or methylation of the promoter region in any of the tumors with the delta A mutation.CONCLUSION:
Although the delta A mutation is a frequent event in sporadic MSI-positive endometrial cancers, it may not be causally associated with defective DNA MMR.
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias do Endométrio
/
Reparo do DNA
Limite:
Female
/
Humans
Idioma:
En
Revista:
J Soc Gynecol Investig
Assunto da revista:
GINECOLOGIA
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos