A panel of repeat markers for detection of microsatellite instability in murine tumors.
A substantial fraction of human malignancies lack functional DNA mismatch repair (MMR), accumulate mutations at high frequency, and exhibit microsatellite instability (MSI). In order to distinguish between MMR-competent and MMR-deficient malignancies, a consensus panel of microsatellite repeats has been adopted for MSI analysis of human tumors. There is no reference panel of repeats for MSI typing of murine malignancies. In this study, we present six new microsatellite repeat markers for MSI typing of mouse tumors. Analysis of polymerase chain reaction (PCR)-amplified tumor DNA from MMR-deficient and -proficient mice on denaturing polyacrylamide gels revealed that the new panel of microsatellites was more sensitive in detecting MSI than six commonly used CA(n) repeats. Using the new set of microsatellite markers, we demonstrated the presence of MSI in endometrial carcinoma and cancer precursors from diethylstilbestrol (DES)-treated mice, pointing to a possible role for loss of MMR in hormonally promoted endometrial tumorigenesis.
Kabbarah
Omar
O
Division of Biology and Biomedical Sciences and Department of Surgery, Washington University in St. Louis, St. Louis, Missouri 63110, USA.
Mallon
Mary Ann
MA
Pfeifer
John D
JD
Edelmann
Winfried
W
Kucherlapati
Raju
R
Goodfellow
Paul J
PJ
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D043171:Chromosomal Instability / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins; D004054:Diethylstilbestrol / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D004717:Endometrium / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D008223:Lymphoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C501486:MLH1 protein, human; C501485:Mlh1 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D004054:Diethylstilbestrol; C497173:Msh2 protein, mouse; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein