Background:
A man’s lifetime risk of developing prostate cancer is approximately 1 in 8. Most cases of prostate cancers develop sporadically; however, an estimated 5-10% of cases are due to a hereditary predisposition. Factors that may be associated with hereditary prostate cancer include: early-onset prostate cancer, multiple family members affected with prostate cancer, or prostate cancer with a family history of other cancers such as breast, ovarian, and pancreatic cancer.
Understanding the molecular etiology of such cancer incidence can help guide treatment and proper surveillance. Our next-generation sequencing test is designed to detect mutations in the coding region of 14 genes associated with inherited prostate cancer, or increasing the risk for cancer onset. Our microarray test is designed to identify single exon deletions and duplications in the same 14 inherited prostate cancer-associated genes. Combining deletion/duplication data analyzed by microarray with next-generation sequencing data will allow KDL to improve diagnostic yield and deliver more comprehensive results.
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 prostate cancer.
- To aid in decision-making for treatment and management of individuals with inherited prostate cancer.
- Testing for individuals with a positive family history for inherited prostate cancer (targeted testing is available if familial mutation is known).
Methodology:
Next generation sequencing will analyze the exons or coding regions of 14 Inherited Prostate Cancer-associated genes using Illumina NextSeq 500/550 technology. Samples are prepared using hybridization probes to enrich exonic regions. This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats, but may contain variants that impact gene function.
Exon-level deletion/duplication analysis is performed by running the NGS data through the Genome Analysis Toolkit (GATK) Germline Copy Number Variation best practices pipeline from GATK, version 4.1.4.1. A Bayesian model was validated clinically in our lab. The model can detect copy changes at a resolution of three (3) or more probe targets (exons) for deletions and duplications in genes that do not have pseudogenes, and is not designed to detect low-level mosaicism or balanced alterations.
The 14 Inherited Prostate Cancer -associated genes are listed below:
ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, TP53
Specimen Requirements:
Blood: EDTA or ACD (Solution A or B):
- Adult: 5 mL
- Child: 5 mL
- Infant: 2-3 mL
Saliva: 2 ORAgene™ Saliva Collection Kits (OGR-500) used according to manufacturer instructions. Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.
Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions. Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.
Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks.
DNA: 10µg at a minimum of 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:
- Familial prostate cancer. Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/4520/familial-prostate-cancer.
- Prostate cancer - Genetics Home Reference - NIH. U.S. National Library of Medicine. https://ghr.nlm.nih.gov/condition/prostate-cancer
Additional Info: