Hereditary Breast Cancer via the CHEK2 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
714 CHEK2$940.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
This test is predicted to detect pathogenic mutations in ~6% of women with non-BRCA1/2 Hereditary Breast Cancer (Nevanlinna & Bartek Oncogene 25:5912-5919, 2006).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 CHEK2$690.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity
Due to known segmental duplications in CHEK2, gross deletions and duplications are only analyzed for exons 8-10.

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Clinical Features

More than 1 million new cases of breast cancer occur each year worldwide, making it the most common malignancy among women. It is estimated that ~10% of these cases have a strong hereditary component. Hereditary Breast Cancer (HBC; OMIM 114480) refers to the familial occurrence of early-onset (prior to the age of 40), bilateral mammary carcinomas. Importantly, tumors from individuals with HBC tend to be of a much higher histological grade, when first detected, than tumors from sporadic age-matched breast cancer controls (Honrado et al. Modern Pathology 18:1305-1320, 2005). As a result, survival rate after treatment is two-fold lower for patients with HBC, compared to those with sporadic breast cancer (Lonning et al. Ann Oncol 18:1293-1306, 2007). Thus, identifying individuals with a high-risk for developing HBC allows for early detection of tumor formation in these individuals, and is predicted to increase the rate of patient survival.


Mutations in a number of genes have been reported to significantly increase an individual’s likelihood for developing breast cancer (reviewed by Tan et al. J Clin Pathol 61:1073-1082, 2008). Among those, germline mutations in the Breast Cancer genes, BRCA1 and BRCA2, appear to provide the highest relative risk, ~10- to 20-fold. Early-onset breast cancer is also a major component of the Li-Fraumeni Syndrome (LFS; OMIM 151623), and mutations in the LFS-associated gene TP53 also provide a 10- to 20-fold increased risk for developing bilateral mammary carcinomas, in addition to other cancers. Mutations in the CHEK2 gene (OMIM 604373) were also reported to cause a Li-Fraumeni-like syndrome (Bell et al. Science 286:2528-2531, 1999), although subsequent studies have indicated that CHEK2 mutations are only very rarely found in patients with classic symptoms of LFS (Lee et al. Cancer Res 61:8062-8067, 2001). However, mutations in CHEK2 have been frequently found in patients who have hereditary breast cancer (HBC) but do not have detectable BRCA1 or BRACA2 mutations (Vahteristo et al. Am J Hum Genet 71:432-438, 2002; Meijers-Heijboer et al. Am J Hum Genet 72:1308-1314, 2003), indicating CHEK2 mutations likely contribute to a significant fraction of non-BRCA1/2 hereditary breast carcinomas. CHEK2 encodes a protein kinase that protects the genome from ionizing radiation and genotoxic insults. To date, approximately 40 mutations have been reported throughout the CHEK2 gene, and >95% are detectable by this DNA sequencing test (Human Gene Mutation Database,

Testing Strategy

This test involves bidirectional DNA sequencing of coding exons 2-16 of the CHEK2 gene, plus ~20 bp of flanking non-coding DNA on either side of each exon. We will also sequence any single exon (Test #100) in family members of patients with a known mutation or to confirm research results.

Indications for Test

This test is recommended for individuals diagnosed with early-onset bilateral mammary carcinomas and a family history of breast cancer and/or sarcomas, particularly those who do not have a detectable mutation in BRCA1, BRCA2 or TP53 genes. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.


Official Gene Symbol OMIM ID
CHEK2 604373
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Familial Cancer Of Breast 114480

Related Tests

Cancer Sequencing and Deletion/Duplication Panel
Colorectal Cancer Sequencing And Deletion/Duplication Panel
Hereditary Breast and Ovarian Cancer Syndrome - HBOC EXPANDED Sequencing and Deletion/Duplication Panel


Genetic Counselors
  • Bell, D. W., (1999). "Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome." Science 286(5449): 2528-31. PubMed ID: 10617473
  • Honrado, E., (2005). "The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications." Mod Pathol 18(10): 1305-20. PubMed ID: 15933754
  • Human Gene Mutation Database.
  • Lee SB, Kim SH, Bell DW, Wahrer DC, Schiripo TA, Jorczak MM, Sgroi DC, Garber JE, Li FP, Nichols KE. 2001. Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome. Cancer research 61: 8062–8067. PubMed ID: 11719428
  • Lonning, P. E., (2007). "Breast cancer prognostication and prediction in the postgenomic era." Ann Oncol 18(8): 1293-306. PubMed ID: 17317675
  • Meijers-Heijboer H, Wijnen J, Vasen H, Wasielewski M, Wagner A, Hollestelle A, Elstrodt F, Bos R van den, Snoo A de, Fat GTA, Brekelmans C, Jagmohan S, et al. 2003. The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. Am. J. Hum. Genet. 72: 1308–1314. PubMed ID: 12690581
  • Nevanlinna, H., Bartek, J. (2006). "The CHEK2 gene and inherited breast cancer susceptibility." Oncogene 25(43): 5912-9. PubMed ID: 16998506
  • Tan DSP, Marchio C, Reis-Filho JS. 2008. Hereditary breast cancer: from molecular pathology to tailored therapies. Journal of Clinical Pathology 61: 1073–1082. PubMed ID: 18682420
  • Vahteristo P, Bartkova J, Eerola H, Syrjäkoski K, Ojala S, Kilpivaara O, Tamminen A, Kononen J, Aittomäki K, Heikkilä P, Holli K, Blomqvist C, et al. 2002. A CHEK2 Genetic Variant Contributing to a Substantial Fraction of Familial Breast Cancer. American Journal of Human Genetics 71: 432. PubMed ID: 12094328
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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