SALSA MLPA P083 CDH1 probemixCEimproved

application: Hereditary diffuse gastric cancer
region: CDH1 at 16q22.1
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version: D1
sold since: 2017-09-18

item no. description price
P083-025R SALSA MLPA P083 CDH1 probemix – 25 rxn € 237
P083-050R SALSA MLPA P083 CDH1 probemix – 50 rxn € 474
P083-100R SALSA MLPA P083 CDH1 probemix – 100 rxn € 948
EK1-FAM SALSA MLPA EK1 reagent kit – 100 rxn - FAM € 294
EK1-Cy5 SALSA MLPA EK1 reagent kit – 100 rxn - Cy5 € 294
EK5-FAM SALSA MLPA EK5 reagent kit – 500 rxn - FAM € 1355
EK5-Cy5 SALSA MLPA EK5 reagent kit – 500 rxn - Cy5 € 1355

Please note that both a probemix and reagent kit are needed to perform MLPA.

description
Intended use: The SALSA MLPA probemix P083 CDH1 is an in vitro diagnostic (IVD)1 or a research use only (RUO) assay for the detection of deletions or duplications in the human CDH1 gene in order to confirm a potential cause and clinical diagnosis for hereditary diffuse gastric cancer. This product can also be used for molecular genetic testing of at-risk family members.

This assay is for use with human DNA extracted from peripheral blood. Deletions and duplications detected with the P083 CDH1 probemix must be verified by another technique. In particular, deletions or duplications detected by only a single probe always require validation by another method. Most defects in the CDH1 gene are point mutations, none of which will be detected by MLPA. It is therefore recommended to use this SALSA MLPA probemix in combination with sequence analysis of CDH1. This assay is not intended to be used as a standalone assay for clinical decisions. The results of this test should be interpreted by a clinical molecular geneticist or equivalent.
This probemix can be used on gastric and breast tumour tissue to detect deletions and duplications in a research setting.

1Please note that this probemix is for In Vitro Diagnostic use (IVD) in the countries specified at the end of this product description. In all other countries, the product is for Research Use Only (RUO).

Clinical background: Germline heterozygous mutations in the CDH1 gene have been reported in approximately 45% of families with a hereditary predisposition to diffuse gastric cancer (Oliveira et al. 2013). CDH1 or E-cadherin is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium dependent cell-cell adhesion glycoprotein. Reduced expression of E-cadherin is regarded as one of the main molecular events involved in dysfunction of the cell-cell adhesion system, triggering cancer invasion and metastasis. Hereditary diffuse gastric cancer (HDGC) accounts for <1% of all gastric cancer patients (Sugimoto et al. 2015). The majority of the cancers in individuals with a CDH1 pathogenic variant occur before the age of 40. The penetrance of HDGC is incomplete and the estimated cumulative risk of gastric cancer by age 80 years is 80% for both men and women. Women also have a 39%-52% risk for developing lobular breast cancer. If gastric cancer is detected early and is resected, the 5-year survival rate can be greater than 90%. However, HDGC has an infiltrative growth pattern and is difficult to diagnose. Once symptoms appear, affected individuals are in an advanced stage of the disease with a poor prognosis, with a 5-year survival rate lower than 20% (Oliveira et al. 2013). Therefore, clinical management options for carriers of germline CDH1 mutations include prophylactic gastrectomy and/or an intensive regimen of endoscopic surveillance. However, the value of a surveillance regime is not yet proven, as in most cases the gastric cancer is not detected until it reaches an incurable, advanced stage. In addition, for women carrying a CDH1 mutation, regular breast screening is recommended (Oliveira et al. 2013). Lobular breast cancer can be the first manifestation of HDGC, also in patients without a history of gastric cancer (Benusiglio et al. 2013). More information on HDGC is available at: https://www.ncbi.nlm.nih.gov/books/NBK1139/.

P083-D1 probemix content: This SALSA MLPA probemix P083 CDH1 contains 37 MLPA probes with amplification products between 126 and 409 nt (Table 1), including 15 reference probes. At least one MLPA probe is present for each exon of CDH1; two probes are present for exon 2 and for exon 16, and there is one probe for the sequence upstream and one probe for the sequence downstream of CDH1 (Table 2a). In addition, two probes targeting flanking genes (one upstream and one downstream of CDH1), are included to help determine the extent of a deletion/duplication. The identity of the genes detected by the reference probes is available in Table 2b and online (www.mlpa.com).

This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity Fragments (Q-fragments), three DNA Denaturation Fragments (D-fragments), and one chromosome X and one chromosome Y-specific fragment (Table 1). The Q-fragments are only visible when less than 100 ng sample DNA is used. Low signal of the 88 and 96 nt fragments indicates incomplete DNA denaturation. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol.

product history
version D1: Five CDH1 probes have been replaced, three have been added, and two new flanking probes have been included. Several reference probes have been removed or replaced. Several probes have a small change in length but not in the sequence detected.
version C2: Five reference probes have been replaced.
version C1: As compared to previous B1 version, new in version C1: two CDH1 probes and several reference probes have been replaced/added. In addition, the 88 and 96nt control fragments have been replaced (QDX2).
version B1: Five CDH1 probes and six reference probes have been replaced.
version A2: Extra control fragments at 88-96-100-105 nt have been added and 5 probes have a slightly different length and / or peak height. No change in sequences detected.

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