| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-97 |
DRI_Background |
denotes |
Genomic rearrangements in MSH2, MLH1 or MSH6 are rare in HNPCC patients carrying point mutations. |
| T2 |
98-299 |
DRI_Background |
denotes |
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease with high penetrance, caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, PMS2 and MLH3. |
| T3 |
300-425 |
DRI_Approach |
denotes |
Most reported pathogenic mutations are point mutations, comprising single base substitutions, small insertions and deletions. |
| T4 |
426-673 |
DRI_Background |
denotes |
In addition, genomic rearrangements, such as large deletions and duplications not detectable by PCR and Sanger sequencing, have been identified in a significant proportion of HNPCC families, which do not carry a pathogenic MMR gene point mutation. |
| T5 |
674-927 |
DRI_Background |
denotes |
To clarify whether genomic rearrangements in MLH1, MSH2 or MSH6 also occur in patients carrying a point mutation, we subjected normal tissue DNA of 137 colorectal cancer (CRC) patients to multiplex ligation-dependent probe amplification (MLPA) analysis. |
| T6 |
928-1175 |
DRI_Outcome |
denotes |
Patients fulfilled the following pre-requisites: all patients met at least one criterion of the Bethesda guidelines and their tumors exhibited high microsatellite instability (MSI-H) and/or showed loss of expression of MLH1, MSH2 or MSH6 proteins. |
| T7 |
1176-1583 |
DRI_Background |
denotes |
PCR amplification and Sanger sequencing of all exons of at least one MMR gene, whose protein expression had been lost in the tumor tissue, identified 52 index patients without a point mutation (Group 1), 71 index patients with a pathogenic point mutation in MLH1 (n=38) or MSH2 (n=22) or MSH6 (n=11) (Group 2) and 14 patients with an unclassified variant in MLH1 (n=9) or MSH2 (n=3) or MSH6 (n=2) (Group 3). |
| T8 |
1584-1663 |
DRI_Background |
denotes |
In 13 of 52 patients of group 1 deletions of at least one exon were identified. |
| T9 |
1664-1720 |
DRI_Background |
denotes |
In addition, in group 3 one EX1_15del in MLH1 was found. |
| T10 |
1721-1781 |
DRI_Background |
denotes |
No genomic rearrangement was identified in group 2 patients. |
| T11 |
1782-1895 |
DRI_Background |
denotes |
Genomic rearrangements represent a significant proportion of pathogenic mutations of MMR genes in HNPCC patients. |
| T12 |
1896-1987 |
DRI_Background |
denotes |
However, genomic rearrangements are rare in patients carrying point mutations in MMR genes. |
| T13 |
1988-2101 |
DRI_Background |
denotes |
These findings suggest the use of genomic rearrangement tests in addition to Sanger sequencing in HNPCC patients. |
