A clinical questionnaire should be submitted with all specimens. Contact CMBP genetics services at 800-345-4363 to coordinate testing.
Expected Turnaround Time
14 - 24 days
Turnaround time is defined as the usual number of days from the date of pickup of a specimen for testing to when the result is released to the ordering provider. In some cases, additional time should be allowed for additional confirmatory or additional reflex tests. Testing schedules may vary.
Whole blood, saliva collected in an Oragene Dx collection kit
7 mL whole blood, 2 mL saliva
3 mL whole blood, 0.5 mL saliva
Lavender-top (EDTA) tube or yellow-top (ACD) tube
Blood is collected by routine phlebotomy. Saliva is collected by spitting into the provided container until it reaches the fill line.
Maintain specimen at room temperature
Causes for Rejection
Frozen whole blood, serum or marrow; leaking tube; clotted blood or marrow; grossly hemolyzed specimen; incorrect anticoagulant
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.
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.
Next generation sequencing and multiplex ligation-dependent probe amplification (MLPA) platform
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.