Hypothesis: Possible role of retinoic acid therapy in patients with biallelic mismatch repair gene defects.

A boy showing symptoms of a Turcot-like childhood cancer syndrome together with stigmata of neurofibromatosis type I is reported. His brother suffers from an infantile myofibromatosis, and a sister died of glioblastoma at age 7. Another 7-year-old brother is so far clinically unaffected.

A complex rearrangement in the APC gene uncovered by multiplex ligation-dependent probe amplification.

Germline mutations in the tumor suppressor gene APC are the underlying cause of familial adenomatous polyposis, an autosomal-dominant cancer predisposition syndrome of the colorectum. Here, we describe a complex pathogenic rearrangement in the APC gene that was detected during deletion screening and transmitted throughout at least three generations. The rearrangement consists of a deletion of 604 bp in intron 4 that impairs the binding site of the reverse primer for exon 4 and of an insertion of 119 bp in exon 4 that interferes with the binding site of the multiplex ligation-dependent probe amplification (MLPA) probes for exon 4.

The additive effect of p53 Arg72Pro and RNASEL Arg462Gln genotypes on age of disease onset in Lynch syndrome patients with pathogenic germline mutations in MSH2 or MLH1.

p53 and the prostate-cancer-susceptibility gene RNASEL are tumour suppressor genes involved in apoptosis. We have previously reported that the common, functionally different variants Arg72Pro in p53 and Arg462Gln in RNASEL are associated with the age of disease onset of colorectal cancer in Lynch syndrome patients. To assess the combined effect of both variants, we screened 246 unrelated Lynch syndrome patients with a pathogenic germline mutation either in MSH2 (n=138) or in MLH1 (n=108) and colorectal cancer as first tumour, and 245 healthy controls.

Frequency of hereditary non-polyposis colorectal cancer among unselected patients with colorectal cancer in Germany.

Introduction: Hereditary non-polyposis colorectal cancer (HNPCC) is a major form of familial colorectal cancer (CRC). It is diagnosed when either the Amsterdam criteria (AC) are fulfilled or mutations in one of the mismatch repair (MMR) genes have been identified. This project aims at estimating the proportion of HNPCC among unselected patients with CRC.