Mutations in DNA mismatch repair genes are not responsible for microsatellite instability in most sporadic endometrial carcinomas.
Endometrial carcinoma is the second most common tumor type in women with hereditary nonpolyposis colorectal carcinoma. Microsatellite instability (MI) has been observed in the inherited (hereditary nonpolyposis colorectal carcinoma-associated) form of endometrial carcinoma as well as in approximately 20% of presumably sporadic cases. Recent studies suggest that MI in many cell lines or xenografts derived from sporadic colorectal carcinomas is not attributable to mutations in four known human DNA mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, and hPMS2). Mutational analyses of these four MMR genes in endometrial carcinomas have not been previously reported. We analyzed nine sporadic MI-positive primary endometrial carcinomas for mutations in the above four MMR genes. Mutations were detected in two tumors (in hMSH2), and both of the mutations were acquired somatically. Immunohistochemical staining revealed a lack of expression of hMSH2 protein in the two tumors containing hMSH2 mutations. Our data suggest that mutations in these four known DNA MMR genes are not responsible for MI in the majority of sporadic endometrial carcinomas displaying this phenotype.
Katabuchi
H
H
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
van Rees
B
B
Lambers
A R
AR
Ronnett
B M
BM
Blazes
M S
MS
Leach
F S
FS
Cho
K R
KR
Hedrick
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D004252:DNA Mutational Analysis; D015342:DNA Probes / Q000737:chemistry; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004276:DNA, Satellite / Q000235:genetics*; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D011519:Proto-Oncogenes / Q000235:genetics*
D015342:DNA Probes; D004273:DNA, Neoplasm; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein