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SALSA® MLPA® Probemix P190 CHEK2 detects copy number variations in the CHEK2, ATM and TP53 genes.
Contents: 53 MLPA probes, including 19 probes for CHEK2 region (covering all 15 exons), 1 probe for the CHEK2 c.1100delC mutation, 19 probes for ATM and 4 probes for TP53.
Tissue: genomic DNA isolated from human peripheral whole blood.
Application: breast cancer (negative for BRCA1, BRCA2 and PALB2 mutations) and CHEK2-related cancer types.
CE-marked and registered for in vitro diagnostic (IVD) use in selected territories.
The SALSA MLPA Probemix P190 CHEK2 is an in vitro diagnostic (IVD) or research use only (RUO) semi-quantitative assay for the detection of deletions or duplications in the human CHEK2, ATM and TP53 genes, and for the detection of the CHEK2 c.1100delC variant in genomic DNA isolated from human peripheral whole blood specimens. P190 CHEK2 is intended to confirm a potential cause for breast cancer in patients who are negative for BRCA1, BRCA2 and PALB2 mutations, and for other CHEK2-related cancer types, including colorectal cancer. This product can also be used to determine increased cancer susceptibility in at-risk family members.
For the full intended purpose, see the product description.
CHEK2, ATM and TP53 all play important roles in DNA damage repair. A defect in one of these genes can lead to an increased risk of tumour formation. For breast cancer, autosomal dominant mutations in the genes BRCA1 and BRCA2 are the most frequent cause, followed by mutations in CHEK2, ATM and PALB2, though with a much lower frequency (Buys et al. 2017). Mutations in CHEK2 may also increase the risk of developing colorectal cancer (Xiang et al. 2011) and other cancers, including prostate cancer (Cybulski et al. 2006). Mutations in CHEK2, and the c.1100delC mutation in particular, have also been suggested as an underlying cause of Li-Fraumeni syndrome (LFS) type 2. Moreover, a deletion in CHEK2 was found in a patient fulfilling Li-Fraumeni-Like (LFL) criteria (Ruijs et al. 2009). Researchers are uncertain whether CHEK2 mutations actually cause LFS or are merely associated with an increased risk of several types of cancer, including cancers seen in LFS. For more information: https://omim.org/entry/609265.
CHEK2 exons 11-15 share a high sequence homology with several CHEK2 pseudogenes, which can result in a pseudogene-mediated gene conversion (Pan et al. 2017).
Autosomal dominant mutations in ATM are linked to an increased risk of cancer, with breast cancer in particular (see Table 1). Autosomal recessive mutations of ATM cause Ataxia-Telangiectasia, which is characterized by progressive cerebellar ataxia, telangiectases, and a predisposition to malignancy, particularly leukaemia and lymphoma. For more information: https://www.ncbi.nlm.nih.gov/books/NBK26468/.
Autosomal dominant TP53 mutations result in LFS. The most common types of tumours in LFS are soft tissue sarcomas and osteosarcomas, pre-menopausal breast cancer, brain tumours, leukaemia, and adrenocortical carcinoma. Families presenting incomplete features of LFS are referred to as having LFL, and around 20-40% of these patients have a germline mutation in TP53 (Ruijs et al. 2010). More information on LFS: https://www.ncbi.nlm.nih.gov/books/NBK1311/.
Gene | Cancer | Relative risk | Occurrence mutations* | References# |
---|---|---|---|---|
CHEK2 | Breast | Lifetime risk of 25-39% in heterozygotes, dependent on the variant and family history | 0-3.5% depending on ethnicity | PMID: 18172190, 21876083, 18381420, 28085182, 15122511, 27595995 |
Other cancers, such as colorectal and prostate | Only preliminary evidence | Not known | PMID: 21807500, 25431674, 17085682, 24506336, 22901170 | |
ATM | Breast | Lifetime risk of 17-52%, but can be dependent on the variant | ~1% | PMID: 26523341, 28085182, 16832357, 19781682, 22585167, 27595995 |
Other cancers, such as pancreatic, ovarian and prostate | Only preliminary evidence | Not known | PMID: 22585167, 26483394, 27433846, 18565893, 29348823, 29486991 | |
TP53 | (Pre-menopausal) Breast | Lifetime risk of ~79% | <1% | PMID: 20522432, 28085182, 25467110, 26523341 |
Other cancers, such as sarcomas and brain tumours | Lifetime risk of cancer in general for men is 73%; for women this is nearly 100% | ~80% of families with features of LFS | PMID: 10864200, 20522432 |
* Including point mutations, indels, deletions and duplications. Percentages depend on the population tested. For example, these percentages may be higher in a BRCA1/2 mutation negative population.
# PMID: PubMed unique identifier.
SALSA MLPA Probemix P190 CHEK2 is CE-marked for in vitro diagnostic (IVD) use. This assay has also been registered for IVD use in Israel.
This assay is for research use only (RUO) in all other territories.
SALSA Binning DNA SD078 is an artificial DNA sample with a signal for all probes in the P190 CHEK2 probemix. Inclusion of a reaction with SD078 in initial experiments and in experiments following a change in electrophoresis conditions is recommended to aid in the creation of a bin set that links peaks to the probes that produce them. Binning DNA cannot be used as a reference sample in the MLPA data analysis, and cannot be used to quantify the signals of mutation-specific probes.
A vial of SALSA Binning DNA SD078 is included with every order of the P190 CHEK2 probemix, but it is possible to order additional vials separately.
For more information, see the product description.
A general SALSA MLPA Reagent Kit is required for MLPA experiments (to be ordered separately).
A vial is included with every order of this probemix, but additional vials can also be purchased separately.
Inclusion of a positive sample is usually not required, but can be useful for the analysis of your experiments. MRC Holland has very limited access to positive samples and cannot supply such samples. We recommend using positive samples from your own collection. Alternatively, you can use positive samples from an online biorepository, such as the Coriell Institute.
See this support article for commercially available positive samples that have been tested with this product.