Background:

Hereditary breast and ovarian cancer (HBOC) due to mutations in the BRCA1 and BRCA2 genes is the most common cause of hereditary forms of both breast and ovarian cancer and occurs in all ethnic and racial populations and mutations in the BRCA1 and BRCA2 genes are inherited in an autosomal dominant manner. The overall prevalence of BRCA1/2 mutations is estimated to be from 1 in 400 to 1 in 800 with a higher prevalence in the Ashkenazi Jewish population (1 in 40). Estimates of penetrance have been shown to vary within families with the same BRCA1/2 mutation (Petrucelli et al, 2010).

The results from genetic tests can facilitate assessment of levels of risk for patients and lead to more efficient and appropriate medical management. It is recommended that this testing be accompanied by a complete family history and genetic counseling.

Reasons for Referral:

  • Confirmation of a clinical diagnosis of an inherited cancer.
  • Testing for individuals with a positive family history for inherited cancer (targeted testing is available if familial mutation is known).

Methodology:

This test has two components:

Component 1: Sequencing Analysis – Next generation sequencing will analyze the exons or coding regions of the genes using Illumina NextSeq 500 technology and preparing samples using hybridization probes to enrich exonic regions.  Any gaps in coverage in clinically validated genes are completed with traditional Sanger sequencing such that 100% of the coding region of the above genes are covered at 10x coverage or more.  Promoter, intronic, etc. regions are not assessed here but may contain variants that impact gene function.

Component 2: Deletion/Duplication Analysis – A customized CytoSure “exon-centric” array (Oxford Gene Technology) will be used to detect deletions and duplications. The targeted array has enhanced probes targeted to the exonic regions of the medically relevant genes. The arrays will be run using Agilent SureScan technology. This array is an ideal complement to the next generation sequencing approach to provide a comprehensive mutation spectrum analysis for inherited cancer.

Specimen Requirements:

Blood: EDTA or ACD (Solution A or B):

  • Adult: 5 mL
  • Child: 5 mL
  • Infant: 2-3 mL

DNA: 10µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

3 weeks

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

  1. Petrucelli et al, 2010, Genetics in Medicine(2010)12, 245–259.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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