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SALSA MLPA KIT P003 MLH1 / MSH2
Germ-line defects in the DNA mismatch repair genes MSH2 and MLH1, are the major cause of hereditary nonpolyposis colon cancer (HNPCC). Detection of the germ-line defect in HNPCC families allows identification of relatives who require appropriate surveillance and prevents useless surveillance in noncarrier relatives. A significant percentage of the HNPCC germ-line mutations are genomic deletions of one or more exons of the MLH1 and MSH2 genes (Wijnen J.T. et al (1998) Nature Genet. 20: 326-328). In a recent study in which 126 colorectal cancer families were screened, a germ-line mutation was detected in 30% of the families (Gille, J.J.P. et al (2002) British J. of Cancer 87, 892-897). Deletions of one or more MLH1/MSH2 exons were detected with the use of this P003 MLPA kit, and accounted for 46% of all mutations detected (55% of the pathogenic mutations). A wide variety of exon deletions was detected in this study. Apparently, the high percentage of genomic rearrangements found was not due to a small number of founder mutations. This suggests that genomic rearrangements of the MLH1 and MSH2 genes might also be an important cause of HNPCC in other countries. In the study of Gille et al, copy number changes of one or more exons were detected in 17 out of 126 families (13,5%). However, this percentage will depend on the way the cohort is selected. In contrast to MLPA analysis of the BRCA1 gene (Hogervorst et al, 2003) in which several exon deletions as well as exon duplications were identified, no exon duplications were detected in MLH1 and MSH2. The high percentage of gene inactivation due to copy number changes of one or more exons is probably due to the large genomic size of these genes. The MLH1 gene spans 100kb and the MSH2 gene covers 73 Kb. Copy number changes are often mediated by ALU sequences in the introns. The probe mixture included in this kit contains probes for each of the 19 exons of the MLH1 gene and for each of the 17 exons of the MSH2 gene. In addition 7 probes for other human genes located on different chromosomes are included as a controls.
Full mix description (word)
Full mix description (pdf)
Last change in probe mix content: Lot 1006 (October 2006) Current Lot Number.: Lot 0307
IMPORTANT NOTICE: MLPA kits are sold by MRC-Holland for research purposes and to demonstrate the possibilities of the MLPA technique. This kit is not CE/FDA certified for use in diagnostic procedures. Salsa MLPA kits are supplied with all necessary buffers and enzymes. Purchase of the Salsa MLPA test kits includes a limited license to use these products for research purposes. The use of this MLPA kit requires a thermocycler with heated lid and sequence type electrophoresis equipment. Different fluorescent PCR primers are available. The MLPA technique has been first described in Nucleic Acid Research 30, e57 (2002)
References 2007 -- Germline novel MSH2 deletions and a founder MSH2 deletion associated with anticipation effects in HNPCC. Clin Genet. 2007 Feb;71(2):130-139. 2006 --.A missense germline mutation in exon 7 of the MSH2 gene in a HNPCC family from center-Italy. Fam Cancer. 2006 Dec 13. 2006 -- Combined use of MLPA and nonfluorescent multiplex PCR analysis by high performance liquid chromatography for the detection of genomic rearrangements. 2006 -- Genomic rearrangements in MSH2, MLH1 or MSH6 are rare in HNPCC patients carrying point mutations. 2006 -- Identification of mismatch repair gene mutations in young colorectal cancer patients and patients with multiple HNPCC-associated tumours. 2006 -- Zhang J et al. (2006). Gene conversion is a frequent mechanism of inactivation of the wild-type allele in cancers from MLH1/MSH2 deletion carriers. Cancer Res. 2006 Jan 15;66(2):659-64. 2006 -- Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study). 2006 -- The value of multi-modal gene screening in HNPCC in Quebec: three mutations in mismatch repair genes that would have not been correctly identified by genomic DNA sequencing alone. 2006-- Stability of BAT26 in tumours of hereditary nonpolyposis colorectal cancer patients with MSH2 intragenic deletion. 2005-- Frequency of hereditary non-polyposis colorectal cancer among Uruguayan patients with colorectal cancer. 2005-- Deletions Account for 17% of Pathogenic Germline Alterations in MLH1 and MSH2 in Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Families. 2005-- Novel genomic insertion-deletion in MLH1: possible mechanistic role for non-homologous end-joining DNA repair. 2005-- Genomic rearrangements in MSH2 and MLH1 are rare mutational events in Spanish patients with hereditary nonpolyposis colorectal cancer. 2005-- Hereditary nonpolyposis colorectal cancer: pitfalls in deletion screening in MSH2 and MLH1 genes. 2005 -- Analysis of hMLH1 and hMSH2 Gene Dosage Alterations in Hereditary Nonpolyposis Colorectal Cancer Patients by Novel Methods. 2004-- Family cancer histories predictive of a high risk of hereditary non-polyposis colorectal cancer associate significantly with a genomic rearrangement in hMSH2 or hMLH1. 2004-- Dosage analysis of cancer predisposition genes by multiplex ligation-dependent probe amplification. 2003-- Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA. 2003-- Identification and characterization of genomic rearrangements of MSH2 and MLH1 in Lynch Syndrome (HNPCC) by novel techniques. 2002-- Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach.
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