1. Disease-causing gene-flanking genomic rearrangements in HNPCC patients
- Author
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Monika Morak, Trisari Massdorf, Melanie Locher, and Elke Holinski-Feder
- Subjects
Genetics ,congenital, hereditary, and neonatal diseases and abnormalities ,lcsh:QH426-470 ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,digestive system diseases ,DNA sequencing ,Human genetics ,lcsh:Genetics ,Germline mutation ,Oncology ,Fusion transcript ,Poster Presentation ,Medicine ,DNA mismatch repair ,Multiplex ligation-dependent probe amplification ,business ,Gene ,Genetics (clinical) ,Chromosomal inversion - Abstract
Background The molecular diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) or Lynch-Syndrome is the detection of a pathogenic germline mutation in one of the DNA mismatch repair (MMR) genes. However, in ~10-20% of cases suspected of Lynch-syndrome no disease-causing mechanism can be detected. Genomic rearrangements such as gene-flanking deletions, inversions, duplications, or translocations might affect MMR genes - but are difficult to detect. We report here two different disease-causing rearrangement mechanisms in HNPCC patients flanking the gene in question. Material and methods 37 patients with colorectal tumours lacking MMR protein staining were included if gene sequencing and deletion screening did not detect MMR germline mutations. The genomic situation was analyzed by oligo array, MLPA kits (P003, P248, P072) and abnormalities were investigated by Long-Range PCRs and sequencing. Additionally, cDNA analyses were performed. Results
- Published
- 2011