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SALSA MLPA Probemix P045 BRCA2/CHEK2

SALSA® MLPA® Probemix P045 BRCA2/CHEK2 detects copy number variations in the BRCA2 and CHEK2 genes. Copy number variations of BRCA2 can be confirmed with SALSA® MLPA® Probemix P077 BRCA2 Confirmation.

Specifications

Contents: 51 MLPA probes of which 40 probes target BRCA2, including 1 probe detecting the wildtype sequence of the c.156_157insAlu mutation, and 3 probes that target CHEK2, including 1 probe for the c.1100delC mutation.

Tissue: genomic DNA isolated from human peripheral whole blood.

Application: hereditary breast and ovarian cancer (HBOC) syndrome and Fanconi anemia (FA) D1.

CE-marked and registered for in vitro diagnostic (IVD) use in selected territories.

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List Prices Documentation

Key related products

SALSA MLPA Probemix P002 BRCA1

Contains probes for the BRCA1 gene. It should be used for primary screening of BRCA1.

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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MRC Holland has recently obtained the In Vitro Diagnostic Regulation (IVDR; EU 2017/746) certification for this product. The CE-IVDR version will be sold from early 2025, and will be accompanied by a change in the intended purpose. The target testing population for predisposition to breast cancer and other CHEK2-related cancer types will be limited to individuals originally suspected of hereditary breast and ovarian cancer (HBOC) syndrome for the probes targeting CHEK2. In addition, the probes targeting BRCA2 will no longer be intended for diagnostic use related to Fanconi Anemia type D1. The composition of this product remains unchanged.

Compare BRCA2 products from MRC Holland.

Intended purpose

The SALSA MLPA Probemix P045 BRCA2/CHEK2 is an in vitro diagnostic (IVD) or a research use only (RUO) semi-quantitative assay for the detection of deletions or duplications in the BRCA2 gene and the presence of the wildtype sequence of the BRCA2 c.156_157insAlu mutation in genomic DNA isolated from human peripheral whole blood specimens. P045 BRCA2/CHEK2 is intended to confirm a potential cause for and clinical diagnosis of hereditary breast and ovarian cancer (HBOC) syndrome, and, in rare cases, Fanconi Anemia type D1. In addition, deletions and duplications of CHEK2 exon 1 and exon 9 as well as the presence of the CHEK2 c.1100delC mutation can be detected with this probemix in order to confirm a potential cause for breast cancer and other CHEK2-related cancer types. This product can also be used for molecular genetic testing of at-risk family members.

For the full intended purpose, see the product description.

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 for hereditary, versus sporadic, breast cancer are: younger age at diagnosis, frequent bilateral disease, and more frequent occurrence of diseases such as prostate and breast cancer among male relatives. Mutations in the BRCA1 and BRCA2 genes account for about 20-25% of hereditary breast cancers (Easton 1999) and about 5-0% of all breast cancers (Campeau et al. 2008). In addition, mutations in the BRCA1 and BRCA2 genes cause around 15% of ovarian cancers (Pal et al. 2005). Women with a germline BRCA2 mutation have a 45-62% lifetime risk of developing breast cancer, while the risk of women in the general population is 12%. The lifetime risk of developing ovarian cancer in women with a germline BRCA2 mutation is 11-17%, compared to 1-2% in the general population. Deletions and duplications are more frequent for BRCA1 than for BRCA2 in most populations. CNVs in BRCA2 account for 2-3% of all pathogenic BRCA2 mutations, dependent on the population. More information is available at http://www.ncbi.nlm.nih.gov/books/NBK1247/.

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 https://www.ncbi.nlm.nih.gov/books/NBK1401/.

BRCA1 and BRCA2 mutations are the most frequent aberrations 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 CHEK2 c.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).

Regulatory status

SALSA MLPA Probemix P045 BRCA2/CHEK2 is CE-marked for in vitro diagnostic (IVD) use. This assay has also been registered for IVD use in Colombia, Costa Rica and Israel.

This assay is for research use only (RUO) in all other territories.

SALSA Sample DNA for this product

SALSA Binning DNA SD067

SALSA Binning DNA SD067 is an artificial DNA sample with a signal for all probes in the P045 BRCA2/CHEK2 probemix. Inclusion of a reaction with SD067 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 SD067 is included with every order of the P045 BRCA2/CHEK2 probemix, but it is possible to order additional vials separately.

For more information, see the product description.

SALSA Artificial Duplication DNA SD024

SALSA Artificial Duplication DNA SD024 is an artificial DNA sample that will show a duplication for several probes in the P045 BRCA2/CHEK2 probemix. A reaction with SD024 can be used as an artificial positive control, though the use of your own positive samples or commercially available positive samples is recommended if possible.

SD024 is not supplied by default with orders of the P045 BRCA2/CHEK2 probemix, and must be ordered 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
P045-025R
SALSA MLPA Probemix P045 BRCA2/CHEK2 – 25 rxn
MLPA
€ 281.00
P045-050R
SALSA MLPA Probemix P045 BRCA2/CHEK2 – 50 rxn
MLPA
€ 550.00
P045-100R
SALSA MLPA Probemix P045 BRCA2/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
SD067
SALSA Binning DNA SD067 – 6 rxn
MLPA
€ 23.70

Sample DNAs (available separately)

A vial can be ordered separately, but is not included by default with orders of this probemix.

Item no.
Description
Technology
Price
SD024
SALSA Artificial Duplication DNA SD024 – 20 rxn
MLPA
€ 59.00

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.

BRCA2

  • Coriell NA02718: Heterozygous deletion affecting all probes for BRCA2. The downstream flanking probe is also affected.
  • Coriell NA03330: Heterozygous duplication affecting all probes for BRCA2. The downstream flanking probe is also affected.
  • Coriell NA12606: Heterozygous duplication affecting all probes for BRCA2. The downstream flanking probe is also affected.

CHEK2

Resources

General MLPA resources

MLPA education

Publications

Selected publications using P045 BRCA2/CHEK2

  • Apessos A et al. (2018). Comprehensive BRCA mutation analysis in the Greek population. Experience from a single clinical diagnostic center. Cancer Genet. 220:1-12.
  • Apostolou P et al. (2020). BRCA1 and BRCA2 germline testing in Cretan isolates reveals novel and strong founder effects. Int J Cancer. 147:1334-42.
  • Ewald IP et al. (2016). BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome. Genet Mol Biol. 39:223-31.
  • Francies FZ et al. (2015). BRCA1, BRCA2 and PALB2 mutations and CHEK2 c.1100delC in different South African ethnic groups diagnosed with premenopausal and/or triple negative breast cancer. BMC Cancer. 15:912.
  • Han E et al. (2020). Detection of BRCA1/2 large genomic rearrangement including BRCA1 promoter-region deletions using next-generation sequencing. Clin Chim Acta. 505:49-54.
  • Öfverholm A et al. (2023). Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer. BMC Cancer. 23:738.
  • Su L et al. (2018). Prevalence of BRCA1/2 large genomic rearrangements in Chinese women with sporadic triple-negative or familial breast cancer. Clin Genet. 94:165-9.
  • 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.
  • Torres D et al. (2017). Prevalence and Penetrance of BRCA1 and BRCA2 Germline Mutations in Colombian Breast Cancer Patients. Sci Rep. 7:4713.
  • Van der Merwe NC et al. (2020). The contribution of large genomic rearrangements in BRCA1 and BRCA2 to South African familial breast cancer. BMC Cancer. 20:391.

References

  • Campeau PM et al. (2008). Hereditary breast cancer: new genetic developments, new therapeutic avenues. Hum Genet. 124:31-42.
  • Easton DF (1999). How many more breast cancer predisposition genes are there? Breast Cancer Res. 1:14-7.
  • Huijts PEA et al. (2014). CHEK2*1100delC homozygosity in the Netherlands--prevalence and risk of breast and lung cancer. Eur J Hum Genet. 22:46-51.
  • Kriege M et al. (2014). Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy. Br J Cancer. 111:1004-13.
  • Pal T et al. (2005). BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 104:2807-16.
  • Walsh T et al. (2006). Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 295:1379-88.
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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.

CO

IVD-registered in Colombia.

CR

IVD-registered in Costa Rica.

IL

IVD-registered in Israel.