Microsatellite instability in tumor and nonneoplastic colorectal cells from hereditary non-polyposis colorectal cancer and sporadic high microsatellite-instable tumor patients.
Genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) have been frequently studied in various tumor types. Genetic heterogeneity of nonneoplastic cells has not yet been sufficiently investigated. However, genomic instability in normal cells could be a potentially important issue, in particular when these cells are used as reference in LOH and MSI analyses of tumor samples. In order to investigate possible genetic abnormalities in normal colorectal cells of tumor patients, MSI analyses of normal colonic mucosa were performed. Up to 15 different laser-microdissected normal regions containing 50-150 cells were investigated in each of 15 individual microsatellite-stable, sporadic high microsatellite-instable (MSI-H) and hereditary non-polyposis coli cancer (HNPCC) colorectal cancer patients. Frequent MSI and heterogeneity in the MSI pattern were found both in normal and tumor cells from 10 HNPCC and sporadic MSI-H tumor patients whose tumors had defect mismatch repair protein expressions. This observation shows that MSI can also occur in nonneoplastic cells which has to be considered in MSI analyses for molecular HNPCC screening. In addition, considerable genetic heterogeneity was detected in all MSI-H (sporadic and HNPCC) tumors when analyzing five different regions with less than 150 cells, respectively. These differences were not detectable in larger tumor regions containing about 10,000 cells. Thus, heterogeneity of the MSI pattern (e.g. intratumoral MSI) is an important feature of tumors with the MSI-H phenotype.
Dietmaier
W
W
Molecular Pathology Diagnostic Unit, University of Regensburg, Germany. wolfgang.dietmaier@klinik.uni-regensburg.de
Gänsbauer
S
S
Beyser
K
K
Renke
B
B
Hartmann
A
A
Rümmele
P
P
Jauch
K W
KW
Hofstädter
F
F
Rüschoff
J
J
D002469:Cell Separation / Q000295:instrumentation / Q000379:methods; D003106:Colon / Q000737:chemistry / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D004210:Dissection / Q000295:instrumentation / Q000379:methods; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D007834:Lasers; D018895:Microsatellite Repeats / Q000235:genetics*; D012007:Rectum / Q000737:chemistry / Q000378:metabolism / Q000473:pathology