Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary breast and ovarian cancer syndrome.
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 2 genes associated with hereditary breast and ovarian cancer syndrome: BRCA1 and BRCA2.
Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.
BRCA1/2 Full Gene Analysis
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere
with testing.
If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA.
If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Alfa Laboratories for instructions for testing patients who have received a bone marrow transplant.
USEFUL FOR
Evaluation for patients with a personal or family history suggestive of hereditary breast and ovarian cancer (HBOC) syndrome
Establishing a diagnosis of HBOC syndrome allowing for targeted cancer surveillance based on associated risks
Identifying variants within genes known to be associated with increased risk for HBOC syndrome allowing for predictive testing of at-risk family members
Therapeutic eligibility including poly adenosine diphosphate-ribose polymerase (PARP) inhibitors in select cancer types
For more information see Breast, Gynecological and Prostate Cancer Testing Algorithm
Hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominant hereditary cancer syndrome associated with germline variants in the BRCA1 or BRCA2 genes.
Variants within BRCA1 and BRCA2 account for the majority of hereditary breast and ovarian cancer families.(1,2) However, there are additional genes that are known to be associated with hereditary breast and ovarian cancer syndromes.
HBOC syndrome is predominantly characterized by early-onset breast cancer and ovarian cancer. Individuals with breast and ovarian cancer are also at increased risks for prostate, pancreatic, and male breast cancers. Some individuals develop multiple primary or bilateral cancers.(1,2)
Individuals with biallelic pathogenic variants in BRCA1 and BRCA2 are at risk for Fanconi anemia, an autosomal recessive bone marrow failure syndrome. Of note, there are several other genes known to cause Fanconi anemia.(1)
The National Comprehensive Cancer Network and the American Cancer Society provide recommendations regarding the medical management of individuals with HBOC syndrome.(2-4)
All detected variants are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(5)
Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Correlations
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.
Technical Limitations
Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.
There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.
This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Insertions/deletions (indels) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller indels.
Deletion/Duplication Analysis
This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.
This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.
For detailed information regarding gene specific performance and technical limitations, see Method Description or contact our laboratory genetic testing unit at ———————— .
At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time.
Evaluation and categorization of variants is performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline. Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Variants classified as benign or likely benign are not reported.