Hereditary Nonpolyposis Colorectal Cancer (HNPCC), an autosomal dominant susceptibility syndroriie, for approximately 5% of all colorectal tumours. Members of HNPCC families have a predisposition to the of colorectal cancer at an early age and an increased incidence of extracolonic cancer, e.g-, endometrium, ovaries, small bowel, biliary tract, renal pelvis and ureter. Gerrnline mutations in DNA mismatch repair genes, in particular MLI-Il and MSH2, are present in individuals with I-INPCC. Defective DNA mismatch results in genetic instability, which can easily be observed in short repetitive sequences such as microsatellites instability, MSI). MSI has been detected in most MMR-deficient tumours and it is considered the of I-INPCC. An international workshop on MSI held in Bethesda in 1997 proposed a panel of live markers to be used in MSI analysis. This panel, lmown as "Bethesda markers", includes two reats (BAT25, BAT26) and three dinucleotide repeats (D2Sl23, D5S346 and Dl7S250). ln our we are currently using a different microsatellite panel composed by three rnononucleotide repeats (BAT25, BAT40) and two dinucleoide repeats (D2Sl23 and Dl8S57). Aim of our study is to evaluate the speciticity ofr Q Btllhcsda markers, as compared with our panel, to identify MLHI and MSI-I2 mutation-positive HNPCC.We compared the results of MSI~analysis in tumours from 17 HNPCC families (according to and from 75 families in which not all the Amsterdam criteria were met (Suspected HNPCC),both the Bethesda panel and our alternative panel. MSI-H tumours were defined as having instability at two or markers (out of 5), while MSI-L tumours had instability at only one marker and MSS tumours were stable at all In addition, imrrninohistochemistry of MLH1 and MSH2 proteins was performed in all MSI-H and MSI-L to study the correlation between thc two MSI—panels and the expression of MLHI and MSH2 proteins. Results. Using the Bethesda markers, 27 (36%) out of the 75 Suspected HNPCC tumours and I2 (70,6%) out of the HNPCC tumours showed MSI. On the other hand, using our alternative panel, 16 (21.3%) Suspected HNPCC and 7 (41,2%) HNPCC tumours displayed MSI. In Suspected HNPCC tumours we found I5 (20%) md 5 (6.7%) MSI.,using the Bethesda panel and our alternative panel respectively, while in I-INPCC tumours no MSI-L was detected us either panel. Loss of MLHI or MSH2 was evident in 15 out of 39 (38,5%) MSI tumours according to the Beth panel, whereas with our alternative panel 15 out of 23 (65.2%) MSI tumours showed no protein expression.Conclusions. Our data suggest that the Bethesda panel is more sensitive to defne MSI tumours, but the propose marker panel is more sensitive to identify MSI tumours lacking expression of MLHI and MSI-I2 proteins. The marker panel seems to have higher predictive value in the identification of patients with ML!-Il and MSH2 mutations.
|Data di pubblicazione:||2002|
|Titolo:||Two different marker panels for microsatellie instability analysis in detection of constitutional MLH1 and MSH2 mutations.|
|Autori:||Pedroni M.; Borghi F.; Lamberti I.; Scarselli A.; Menigatti M.; Ponti G.; Benatti P.; Losi L.; Di Gregorio C.; Abbati G.; Rossi G.; Roncucci L.; Ponz De Leon M.|
|Autori interni:||PEDRONI, Monica |
PONZ DE LEON, Maurizio
|Nome editore:||not available|
|Appare nelle tipologie:||Monografia/Trattato scientifico|
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