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SALSA MLPA Probemix P190 CHEK2

SALSA® MLPA® Probemix P190 CHEK2 detects copy number variations in the CHEK2, ATM and TP53 genes.

Specifications

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.

Quick links

List Prices Documentation

Key related products

SALSA MLPA Probemix P002 BRCA1

Contains probes for BRCA1, involved in breast and ovarian cancer.

SALSA MLPA Probemix P041 ATM-1

Contains probes for the ATM gene, involved in breast cancer and Ataxia Telangiectasia.

SALSA MLPA Probemix P042 ATM-2

Contains probes for the ATM gene, involved in breast cancer and Ataxia Telangiectasia.

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Intended purpose

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.

Clinical background

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/.

Table 1. Overview of different types of cancer caused by mutations in CHEK2, ATM and TP53, and the associated relative risks of developing these cancers.
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.

Regulatory status

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 Sample DNA for this product

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.

Product documentation

Version D1

Other versions

Contact us for earlier versions.

List prices

Product

Item no.
Description
Technology
Price
P190-025R
SALSA MLPA Probemix P190 CHEK2 – 25 rxn
MLPA
€ 281.00
P190-050R
SALSA MLPA Probemix P190 CHEK2 – 50 rxn
MLPA
€ 550.00
P190-100R
SALSA MLPA Probemix P190 CHEK2 – 100 rxn
MLPA
€ 1075.00

Required reagents

A general SALSA MLPA Reagent Kit is required for MLPA experiments (to be ordered separately).

Item no.
Description
Technology
Price
EK1-FAM
SALSA MLPA Reagent Kit – 100 rxn – FAM (6 vials)
MLPA MS-MLPA
€ 341.00
EK1-Cy5
SALSA MLPA Reagent Kit – 100 rxn – Cy5 (6 vials)
MLPA MS-MLPA
€ 341.00
EK5-FAM
SALSA MLPA Reagent Kit – 500 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 1571.00
EK5-Cy5
SALSA MLPA Reagent Kit – 500 rxn – Cy5 (5×6 vials)
MLPA MS-MLPA
€ 1571.00
EK20-FAM
SALSA MLPA Reagent Kit – 2000 rxn – FAM (5×6 vials)
MLPA MS-MLPA
€ 6037.00

Sample DNAs (included)

A vial is included with every order of this probemix, but additional vials can also be purchased separately.

Item no.
Description
Technology
Price
SD078
SALSA Binning DNA SD078 – 6 rxn
MLPA
€ 23.70

Price details & ordering

The prices above are list prices for direct orders from MRC Holland. Contact us for a quote that takes discounts and additional costs (such as shipping costs) into account. Different prices apply for orders through one of our sales partners; contact your local supplier for a quote.

More information about ordering & prices

Positive samples

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.

The commercially available positive samples below have been tested with the current (D1) version of this product and have been shown to produce useful results.

ATM

CHEK2

  • Coriell HG00187: Positive for the CHEK2 1100delC mutation.
  • Coriell HG00343: Heterozygous deletion affecting the probes for CHEK2 exon 9-10.
  • Coriell HG01872: Heterozygous duplication affecting the probes for CHEK2 exon 3-5.
  • Coriell NA07106: Heterozygous duplication affecting the probes for CHEK2 and HSCB.

Resources

General MLPA resources

MLPA education

Publications

Selected publications using P190 CHEK2

  • Agiannitopoulos K et al. (2023). Copy Number Variations (CNVs) Account for 10.8% of Pathogenic Variants in Patients Referred for Hereditary Cancer Testing. Cancer Genomics Proteomics. 20:448-55.
  • Apostolou P et al. (2021). CHEK2 Pathogenic Variants in Greek Breast Cancer Patients: Evidence for Strong Associations with Estrogen Receptor Positivity, Overuse of Risk-Reducing Procedures and Population Founder Effects. Cancers (Basel). 13:2106.
  • Fostira F et al. (2020). One in three highly selected Greek patients with breast cancer carries a loss-of-function variant in a cancer susceptibility gene. J Med Genet. 57:53-61.
  • Havranek O et al. (2015). Association of Germline CHEK2 Gene Variants with Risk and Prognosis of Non-Hodgkin Lymphoma. PLoS One. 10:e0140819.
  • Lepkes L et al. (2021). Performance of In Silico Prediction Tools for the Detection of Germline Copy Number Variations in Cancer Predisposition Genes in 4208 Female Index Patients with Familial Breast and Ovarian Cancer. Cancers (Basel). 13:118.
  • Nizic-Kos T et al. (2021). Bilateral Disease Common Among Slovenian CHEK2-Positive Breast Cancer Patients. Ann Surg Oncol. 28:2561-70.
  • Nurmi AK et al. (2022). Pathogenic Variant Spectrum in Breast Cancer Risk Genes in Finnish Patients. Cancers (Basel). 14:6158.
  • Rolfes M et al. (2022). Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer. Cancers (Basel). 14:3292.
  • Tedaldi G et al. (2014). First evidence of a large CHEK2 duplication involved in cancer predisposition in an Italian family with hereditary breast cancer. BMC Cancer. 14:478.
  • Tsaousis GN et al. (2019). Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. BMC Cancer. 19:535.
  • Vargas-Parra G et al. (2020). Comprehensive analysis and ACMG-based classification of CHEK2 variants in hereditary cancer patients. Hum Mutat. 41:2128-42.

References

  • Buys SS et al. (2017). A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer. 123:1721-30.
  • Cybulski C et al. (2006). A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer. J Med Genet. 43:863-6.
  • Pan S et al. (2017). Apparent gene conversion event detected in CHEK2 using next generation sequencing analysis. Annual Clinical Genetics Meeting 2017. Poster 156.
  • Ruijs MWG et al. (2009). The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype. Hered Cancer Clin Pract. 7:4.
  • Ruijs MWG et al. (2010). TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet. 47:421-8.
  • Xiang H-P et al. (2011). Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility. Eur J Cancer. 47:2546-51.
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CE

CE-marked products are for In Vitro Diagnostic (IVD) use only in EU (candidate) member states and members of the European Free Trade Association (EFTA), and the UK.

IL

IVD-registered in Israel.