| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-115 |
DRI_Challenge |
denotes |
Assessing how reduced expression levels of the mismatch repair genes MLH1, MSH2, and MSH6 affect repair efficiency. |
| T2 |
116-229 |
DRI_Background |
denotes |
Lynch syndrome (LS), the most common familial colon cancer, is associated with mismatch repair (MMR) malfunction. |
| T3 |
230-379 |
DRI_Background |
denotes |
As mutation carriers inherit one normal and one defected MMR gene allele, cancer risk can be considered as limited amount of normal MMR gene product. |
| T4 |
380-474 |
DRI_Outcome |
denotes |
How reductions in different MMR gene expressions affect MMR capability is, however, not known. |
| T5 |
475-691 |
DRI_Challenge |
denotes |
The in vitro MMR assay is a method for the pathogenicity assessment of MMR gene variants causing functional or expressional defects and thus also suitable to evaluate the effects of reduced expression of normal mRNA. |
| T6 |
692-873 |
DRI_Background |
denotes |
Here, the assay was applied to quantify repair efficiencies of human cells retaining varying expression levels (25%/50%/75%) of the main LS susceptibility genes MLH1, MSH2, or MSH6. |
| T7 |
874-1050 |
DRI_Outcome |
denotes |
Compared with the shRNA knockdown control, already a 50% reduction in mRNA levels could be detected as decreased MMR function although without statistical significance in MLH1. |
| T8 |
1051-1221 |
DRI_Background |
denotes |
In MSH2 and MLH1, total loss of MMR was achieved with 25% expression, whereas in MSH6 and MSH2, the repair capability decreased significantly already with 75% expression. |
| T9 |
1222-1425 |
DRI_Outcome |
denotes |
Our results provide a preliminary indication of relative expressions required for wild-type function and suggest that the in vitro MMR assay could be used to recognize expression levels indicative of LS. |
