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Breast and ovarian cancer, hereditary (HBOC); Susceptibility to breast cancer; Susceptibility to other cancer types

Region: BRCA2 13q13.1; CHEK2 22q12.1

Intended use: The SALSA MLPA probemix P045 BRCA2/CHEK2 is an in vitro diagnostic (IVD)1 or a research use only (RUO) assay for the detection of deletions or duplications in the human BRCA2 gene, and the presence of the c.156_157insAlu mutation, in order to confirm a potential cause and clinical diagnosis for hereditary breast and ovarian cancer (HBOC) or in rare cases Fanconi Anemia type D1. In addition, the 1100delC mutation and deletions or duplications of exon 1 and 9 in CHEK2 can be detected, in order to determine predisposition to breast cancer, but also other cancer types, included but not limited to colon and prostate cancer. This product can also be used for molecular genetic testing of family members who are at risk for the mentioned aberrations.

This assay is for use with human DNA extracted from peripheral blood and not for use with DNA extracted from formalin-fixed paraffin embedded or fresh tumour materials. Deletions or duplications detected with the P045 BRCA2/CHEK2 probemix must be verified by using the SALSA MLPA probemix P077 BRCA2 Confirmation or a different technique. P077 BRCA2 Confirmation cannot be used to verify CHEK2 mutations. However, the P190 CHEK2 probemix is available for deletion or duplication analysis of other CHEK2 exons. Most defects in the BRCA2 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 of the BRCA2 gene. 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.

1Please note that this probemix is for In Vitro Diagnostic (IVD) use 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: Breast and ovarian carcinomas are among the most common malignancies in developed countries. The majority of cases are considered sporadic, but in a substantial portion, a clear history of cases within a family is present. The BRCA1 and BRCA2 proteins are associated with the activation of double-strand break repair and homologous recombination and are important in maintaining genomic stability. Germline mutations in the BRCA1 and BRCA2 genes are linked to a high risk of young-onset hereditary breast and ovarian cancer. Features characteristic of hereditary, versus sporadic, breast cancer are: younger age at diagnosis, frequent bilateral disease, and more frequent occurrence of disease among male relatives. Mutations in the BRCA1 and BRCA2 genes account for about 20 to 25% of hereditary breast cancers (Easton 1999) and about 5 to 10% of all breast cancers (Campeau et al. 2008). In addition, mutations in the BRCA1 and BRCA2 genes cause around 15% of ovarian cancers overall (Pal et al. 2005).

Deletions or duplications are more frequent for BRCA1 than for BRCA2 in most populations. The prevalence of deletions or duplications is dependent on the studied population and ranges from 0% to 11% of all BRCA2 mutations (Agata et al. 2005, Woodward et al. 2005, Casilli et al. 2006, Stadler et al. 2010).

More information is available at

Biallelic pathogenic variants of BRCA2 can result in Fanconi Anemia (FA) type D1. FA is characterized by physical abnormalities (such as short stature or abnormal skin pigmentation), bone marrow failure and increased risk for malignancies. The incidence of FA in general is 1:160,000, of which type D1 comprises around 3% of the cases. FA type D1 is associated with early-onset acute leukaemia and solid tumours. More information on FA is available at

BRCA1 and BRCA2 mutations are most frequently found, but other genes are also associated with an increased risk for developing breast and ovarian cancer, including CHEK2. The protein CHK2 is a cell cycle checkpoint regulator and a putative tumour suppressor. In non-BRCA1/2 breast cancer families, patients heterozygous for the 1100delC mutation have a two times increased risk of developing breast cancer and have a higher contralateral breast cancer rate (Huijts et al. 2014, Kriege et al. 2014). A deletion of exon 9 and 10 in CHEK2 has been found mainly in Slavic populations and is associated with a two times higher risk for breast cancer (Walsh et al. 2006).

Probemix content:
The SALSA MLPA Probemix P045-D1 BRCA2/CHEK2 contains 51 MLPA probes with amplification products between 130 and 500 nucleotides (nt). This includes 40 probes for the BRCA2 region and three probes for the CHEK2 region. In addition, eight reference probes are included that detect autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes are available online (

At least one MLPA probe is present for each exon in the BRCA2 transcript; two probes are present for exons 1 and 3, three probes are present for exons 10 and 27, and six probes are present for exon 11. One of the probes for exon 3 detects the wild type sequence of the c.156_157insAlu mutation and a reduced signal can point towards the presence of this mutation or a deletion of exon 3. In addition, there is a probe for a sequence upstream and a probe for a sequence downstream of BRCA2.

For the CHEK2 gene, one probe is present for exons 1 and 9. Moreover, one probe specific for the CHEK2 1100delC mutation is included, which will only generate a signal when the mutation is present.

This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at

SALSA Binning DNA SD067: The SD067 Binning DNA provided with this probemix can be used for binning of the CHEK2 1100delC mutation-specific probe (490 nt probe 01772-L01336). SD067 Binning DNA is a mixture of genomic DNA from healthy individuals and plasmid DNA that contains the target sequence detected by the above mentioned probe. Inclusion of one reaction with 5 μl SD067 Binning DNA in initial MLPA experiments is essential as it can be used to aid in data binning of the peak pattern using Coffalyser.Net software. Furthermore, Binning DNA should be included in the experiment whenever changes have been applied to the set-up of the capillary electrophoresis device (e.g. when capillaries have been renewed). Binning DNA should never be used as a reference sample in the MLPA data analysis, neither should it be used in quantification of mutation signal(s), as for this purpose true mutation/SNP positive patient samples or cell lines should be used. It is strongly advised that all samples tested are extracted with the same method and derived from the same source of tissue. For further details, please consult the SD067 Binning DNA product description, available online:

SALSA Artificial Duplication DNA SD024: In case no positive DNA sample is available in your laboratory, an artificial duplication DNA sample for this probemix (catalogue number SD024) can be ordered from MRC-Holland. This SD024 Artificial Duplication DNA will show a duplication of two or more probes when using the following probemixes: P045, P090 and P077 for BRCA2 and P002 and P087 for BRCA1. The SD024 Artificial Duplication DNA is a mixture of human female genomic DNA and a titrated amount of plasmid containing selected probe target sequences. For further details, please consult the SD024 Artificial Duplication DNA product description, available online: This product is for research use only (RUO).

Probemix Gene 1 Gene 2 Coverage Use for Remarks
P045 BRCA2/CHEK2 BRCA2 CHEK2 BRCA2: Each exon.
CHEK2 Exon 1, 9, 1100delC mutation (exon 11)
Initial testing Identical BRCA2 probes as P090
P090 BRCA2 BRCA2 - Each exon Initial testing Identical BRCA2 probes as P045
P077 BRCA2 Confirmation BRCA2 - Each exon Confirmation BRCA2 probes target different ligation sites than probes in P090/P045

Sample DNA
Sample DNA developed for this product:


Order Items


Item no.
SALSA MLPA Probemix P045 BRCA2/CHEK2 – 25 rxn
€ 243.00
SALSA MLPA Probemix P045 BRCA2/CHEK2 – 50 rxn
€ 486.00
SALSA MLPA Probemix P045 BRCA2/CHEK2 – 100 rxn
€ 972.00

Required Reagents

Item no.
SALSA MLPA EK1 reagent kit – 100 rxn – FAM
€ 300.00
SALSA MLPA EK1 reagent kit – 100 rxn – Cy5
€ 300.00
SALSA MLPA EK5 reagent kit – 500 rxn – FAM
€ 1380.00
SALSA MLPA EK5 reagent kit – 500 rxn – Cy5
€ 1380.00
SALSA MLPA EK20 reagent kit – 2000 rxn – FAM
€ 5295.00

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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).


IVD-registered in Colombia.


IVD-registered in Costa Rica.


IVD-registered in Israel.


IVD-registered in Morocco.