Hereditary Breast and Ovarian Cancer via the RAD50 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 4649 | RAD50 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Hereditary breast and ovarian cancer (HBOC) syndrome is an inherited disorder that is mainly associated with tumors of the breasts and ovaries. Other malignancies in HBOC families can include melanoma, pancreatic and prostate cancer. In comparison to sporadic breast and ovarian cancers, HBOC syndrome tends to occur at an earlier age (i.e. < 50 years), tumors often occur bilaterally, consist of multiple affected family members, including males with breast cancer, and occurs with a higher predisposition in specific ethnicities, such as the Ashkenazi Jewish population (Petrucelli et al. 2013; Pruthi et al. 2010). Identifying individuals with a high risk for developing HBOC may allow for early detection of tumor formation and allow for prophylactic mastectomy and/or oophorectomy or other treatments (Smith 2012). Breast and ovarian cancers can show familial inheritance due to shared environment or inherited genes of low penetrance, which confer a moderate risk (Berliner et al. 2012). In addition, approximately 5-10% of breast and 10-15% of ovarian cancer cases are the result of genetic predisposition due to gene specific mutations that significantly increase an individual's risk of developing these cancers (Marchina 2010). HBOC syndrome is mainly due to mutations in the BRCA1 and BRCA2 genes, however, pathogenic variants have also been found in other genes.
Genetics
HBOC is inherited in an autosomal dominant manner and presents with incomplete penetrance. The DNA repair protein RAD50, encoded by the RAD50 gene, interacts with the MRE11A and NBS proteins, and is involved in DNA repair via the nonhomologous end joining pathway. In addition to DNA repair, RAD50 is involved in cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. RAD50 pathogenic variants have been found to confer an increased risk of breast and ovarian cancer (Heikkinen et al. 2005; Tommiska et al. 2006; Walsh et al. 2011). The most prominent RAD50 mutations are missense and nonsense variants, but other sequence changes such as splice site, small insertions and deletions have also been reported (Human Gene Mutation Database).
Clinical Sensitivity - Sequencing with CNV PG-Select
Clinical sensitivity is low because HBOC has multiple underlying causes including environment and genetics, and RAD50 pathogenic variants have only been reported in a minority of cases (Tommiska et al. 2006).
Testing Strategy
This test provides full coverage of all coding exons of the RAD50 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Individuals with a clinical presentation or family history of Hereditary Breast and Ovarian Cancer and have tested negative for BRCA1 and BRCA2 gene mutations. Males with breast cancer, and individuals with an Ashkenazi descent with a concern for HBOC should also be tested. Earlier detection of clinical abnormalities may lead to earlier treatment and better outcomes. Similar to BRCA mutation testing, this is a predictive test and provides only information regarding the likelihood of breast and/or ovarian cancer. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Individuals with a clinical presentation or family history of Hereditary Breast and Ovarian Cancer and have tested negative for BRCA1 and BRCA2 gene mutations. Males with breast cancer, and individuals with an Ashkenazi descent with a concern for HBOC should also be tested. Earlier detection of clinical abnormalities may lead to earlier treatment and better outcomes. Similar to BRCA mutation testing, this is a predictive test and provides only information regarding the likelihood of breast and/or ovarian cancer. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| RAD50 | 604040 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Familial Cancer Of Breast | AD | 114480 |
| Nijmegen Breakage Syndrome-Like Disorder | 613078 |
Related Tests
Citations
- Berliner JL, Fay AM, Cummings SA, Burnett B, Tillmanns T. 2012. NSGC Practice Guideline: Risk Assessment and Genetic Counseling for Hereditary Breast and Ovarian Cancer. Journal of Genetic Counseling 22: 155–163. PubMed ID: 23188549
- Heikkinen K, Rapakko K, Karppinen SM, Erkko H, Knuutila S, Lundán T, Mannermaa A, Børresen-Dale AL, Borg A, Barkardottir RB, Petrini J, Winqvist R.. 2005. RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability. Carcinogenesis 27: 1593–1599. PubMed ID: 16474176
- Human Gene Mutation Database (Bio-base).
- Marchina E, Fontana MG, Speziani M, Salvi A, Ricca G, Di Lorenzo D, Gervasi M, Caimi L, Barlati S. 2010. BRCA1 and BRCA2 genetic test in high risk patients and families: counselling and management. Oncology Reports 24: 1661-1667. PubMed ID: 21042765
- Petrucelli N, Daly MB, Feldman GL. 2013. BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301425
- Pruthi S, Gostout BS, Lindor NM. 2010. Identification and Management of Women With BRCA Mutations or Hereditary Predisposition for Breast and Ovarian Cancer. Mayo Clinic Proceedings 85: 1111–1120. PubMed ID: 21123638
- Smith EC. 2012. An Overview of Hereditary Breast and Ovarian Cancer Syndrome. Journal of Midwifery & Women’s Health 57: 577–584. PubMed ID: 23050669
- Tommiska J, Seal S, Renwick A, Barfoot R, Baskcomb L, Jayatilake H, Bartkova J, Tallila J, Kaare M, Tamminen A. 2006. Evaluation of RAD50 in familial breast cancer predisposition. International Journal of Cancer 118: 2911–2916. PubMed ID: 16385572
- Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, Roeb W, Agnew KJ, Stray SM, Wickramanayake A, Norquist B, Pennington KP, et al. 2011. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proceedings of the National Academy of Sciences 108: 18032–18037. PubMed ID: 22006311
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
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.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
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.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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