FAP /POLYPOSIS COLON CANCER
This SALSA MLPA probemix P043 APC is a research use only (RUO) assay for the detection of exon deletions or duplications in the human APC gene and is not intended to be used as a standalone assay for clinical decisions. Most defects in the APC gene are point mutations, the majority of which will not be detected by MLPA. It is therefore recommended to use this SALSA MLPA probemix in combination with sequence analysis. As the phenotypes of APC and MUTYH-related colorectal cancer overlap, three probes for the MUTYH gene are included in the P043-D1 probemix. Since the MUTYH gene is very small (11 kb), these three probes are expected to detect a substantial part of MUTYH exon deletions and duplications. Complete analysis of copy number changes in the MUTYH gene requires the use of the SALSA P378 MUTYH MLPA probe set. Clinical background: Germline defects in the APC gene are the most frequent cause of a hereditary predisposition to polyposis colon cancer. Mutations in the APC gene are an initiating event also for sporadic colorectal tumour genesis. APC-related colorectal cancer is a dominant trait. Mutations in the MUTYH gene result in a heritable predisposition to colon and stomach cancer. In contrast to the APC gene, MUTYH-associated colorectal cancer should be regarded as an autosomal recessive trait. Polyps caused by mutated MUTYH do not appear until adulthood and are less numerous than those found in patients with APC gene mutations. More information on MUTYH-associated polyposis is available on http://www.ncbi.nlm.nih.gov/books/NBK107219/. Among the various defects in the APC and MUTYH genes that have been found in patients, are deletions and duplications of complete exons, which are usually missed by standard sequence analysis. The MLPA technique can detect most of these deletions and duplications and therefore complements sequence analysis of the APC gene. The expected number of APC chromosomal rearrangements that can be detected with this MLPA probemix is around 6% of all APC mutations in most populations (Kerr, S.E. et al, 2013; Jarry, J. et al. 2011). See below for several publications on probemix P043 APC. P043-D1 probemix content: This SALSA MLPA probemix P043 APC contains 43 MLPA probes with amplification products between 130 and 472 nt: 29 probes for the APC gene, 3 probes for the MUTYH gene and 11 reference probes. At least one MLPA probe is present for each exon in the major APC transcript variant 1. Two probes are present for exon 1 (promoter 1B). Inactivation of this alternative promoter has only recently been linked to familial adenomatous polyposis (Rohlin, A. et al, 2011). Exon 18 has a length of over 8 kb and is detected by nine different probes, two of which detect the wild-type sequences at the 1061 and 1309 mutation hotspots.