BRCAssure: Comprehensive BRCA1/2 Analysis

BRCAssure: Comprehensive BRCA1/2 Analysis

Full sequencing of the BRCA1/2 genes, plus deletion/duplication analysis.  May be used to assess the risk of carrying a BRCA1/2 mutation when there is no known familial mutation.

Test No.

252911

Methodology

Next generation sequencing and multiplex ligation-dependent probe amplification (MLPA) platform

CPT

81162

Specimen

Whole blood

Volume

7 mL

Minimum Volume

3 mL

Container

Lavender-top (EDTA) tube or yellow-top (ACD) tube

 

Special Instructions

A BRCAssure clinical questionnaire should be submitted with specimens. Contact CMBP genetics services at 800-345-4363 to coordinate testing.

Causes for Rejection

Frozen whole blood, serum or marrow; leaking tube; clotted blood or marrow; grossly hemolyzed specimen; incorrect anticoagulant

Storage Instructions

Maintain specimen at room temperature

Use Statement

According to the National Comprehensive Cancer Network®1, testing is indicated if one of the features mentioned below is present in the family: Early-age-onset (age <50 years) breast cancer, including both invasive and ductal carcinoma in situ (DCIS) breast cancers; two breast primaries or breast and ovarian/fallopian tube/primary peritoneal cancer in a single individual or two or more breast primaries or breast and ovarian/fallopian tube/primary peritoneal cancers in close (first-, second-, and third-degree) relatives(s) from the same side of the family; populations at risk (eg, Ashkenazi Jewish); member of a family with a known BRCA1 or BRCA2 mutation; any male breast cancer; ovarian/fallopian tube/primary peritoneal cancer at any age.

Limitations

The entire gene coding region of BRCA1/BRCA2 genes, as well as all flanking noncoding regions, is analyzed by next generation sequencing. The test uses Illumina's TruSeq Custom Amplicon approach for target enrichment and MiSeq instrument for sequencing. It is a custom designed pool comprised of 150 oligonucleotide probe pairs for the binding and amplification of products ranging from 220bp to 280bp. Sequencing does not detect inversions, or other rearrangements.


Comprehensive deletion/duplication testing for BRCA1/BRCA2 is performed by using the multiplex ligation-dependent probe amplification (MLPA) platform. The MLPA will detect full BRCA1/BRCA2 gene deletions and multiple- and single-exon deletions and duplications. Balanced translocations are not detected by the method.

References

American Society of Clinical Oncology. American Society of Clinical Oncology Policy Statement Update: Genetic testing for cancer susceptibility. J Clin Oncol. 2003 Jun 15; 21(12):2397-2406.PubMed 12692171

 

Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: A combined analysis of 22 studies. Am J Hum Genet. 2003 May; 72(5):1117-1130. PubMed 12677558

 

Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007 Apr 10; 25(11):1329-1333. PubMed 17416853

 

Engert S, Wappenschmidt B, Betz B, et al. MLPA screening in the BRCA1 gene from 1,506 German hereditary breast cancer cases: Novel deletions, frequent involvement of exon 17, and occurrence in single early-onset cases. Hum Mutat. 2008 Jul; 29(7):948-958. PubMed 18431737

 

Ferla R, Calò V, Cascio S, et al. Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol. 2007 Jun; 18(Suppl 6):vi93-vi98. PubMed 17591843

 

Ford D, Easton DF, Stratton M, et al. Genetic heterogeneity and penetrance of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1998 Mar; 62(3):676-689. PubMed 9497246

 

Herman S, Varga D, Deissler HL, Kreienberg R, Deissler H. Medium-sized deletion in the BRCA1 gene: Limitations of Sanger sequencing and MLPA analyses. Genet Mol Biol. 2012 Jan; 35(1):53-56. PubMed 22481874

 

Janavičius R. Founder BRCA1/2 mutations in the Europe: Implications for hereditary breast-ovarian cancer prevention and control. EPMA J. 2010 Sep; 1(3):397-412. PubMed 23199084

 

Kote-Jarai Z, Leongamornlert D, Saunders E, et al. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: Implications for genetic testing in prostate cancer patients. Br J Cancer. 2011 Oct 11; 105(8):1230-1234. PubMed 21952622

 

National Comprehensive Cancer Network. Clinical practice guidelines in oncology, genetic/familial high-risk assessment: breast and ovarian. Available at: www.nccn.org. 2010. Accessed May 29, 2013

 

Roy R, Chun J, Powell SN. BRCA1 and BRCA2: Different roles in a common pathway of genome protection. Nat Rev Cancer. 2011 Dec 23;12(1):68-78. PubMed 22193408

 

Tai YC, Domchek S, Parmigiani G, Chen S. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007 Dec 5; 99(23):1811-1814. PubMed 18042939

 

Thompson D, Easton DF; Breast Cancer Linkage Consortium. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002 Sep 18: 94(18): 1358-1365. PubMed 12237281

 

Tulinius H, Olafsdottir GH, Sigvaldason H, et al. The effect of a single BRCA2 mutation on cancer in Iceland. J Med Genet. 2002 Jul; 39(7):457-462. PubMed 12114473

 

 

1. National Comprehensive Cancer Network. Clinical practice guidelines in oncology, genetic/familial high-risk assessment: breast and ovarian. Available at: www.nccn.org. 2010. Accessed May 29, 2013.

CPT Codes

The CPT codes included in this publication are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients; however, correct coding often varies from one carrier to another, and LabCorp may bill specific carriers using codes other than those shown. Clients who bill for services should verify the code(s) with the applicable payor to confirm that their use is appropriate in each case.

Profile Policy

LabCorp's policy is to provide physicians, in each instance, with the flexibility to choose appropriate tests to assure that the convenience of ordering test combinations/profiles does not prevent physicians who wish to order a test combination/profile from making deliberate informed decisions regarding which tests are medically necessary. All the tests offered in test combinations/profiles may be ordered individually using the LabCorp test request form.

Please remember that (1) when ordering tests for which Medicare or Medicaid reimbursement is sought, the physician should only order those tests that the physician believes are medically necessary for each patient, (2) that using a customized profile may result in ordering tests for which Medicare or Medicaid will deny payment, (3) that the physician should only order individual tests or a less inclusive profile where not all the tests in the customized test combination/profile are medically necessary for an individual patient, and (4) that the United States Department of Health and Human Services, Office of Inspector General, takes the position that a physician who orders medically unnecessary tests may be subject to civil penalties.

LabCorp encourages clients to contact their local LabCorp representative or LabCorp location if the testing configurations shown here do not meet individual needs for any reason, or if some other combination of procedures is desired.

Investigational Procedures

Some of the individual tests and profile test components listed in this Directory may be considered by Medicare or other insurance carriers as investigational procedures, and therefore, the test may not be payable by the carrier as a covered benefit for the patient. Medicare patients must be informed of this possibility when the physician orders tests that may fall into this category. Affected patients must be asked to sign an Advance Beneficiary Notice, agreeing to be financially responsible if the service is denied by the carrier. Additionally, for other insurance plans, physicians should inform the patient that the service(s) may not be covered by their private insurance plan and, if so, they will be financially responsible for payment. If the patient declines to accept financial responsibility, please do not order the test(s).

As with all clinical assays, results of these tests should be used only in conjunction with other medically established diagnostic elements (eg, symptoms, history, clinical impressions, results from other tests, etc). Physicians should use all the information available to them to diagnose and determine appropriate treatment for their patients. In order to obtain a current list of the procedures that may be considered investigational by Medicare or other insurance carriers, please contact your local LabCorp representative.