The Prostate Cancer Panel is a comprehensive next-generation sequencing (NGS) panel that analyzes genes associated with increased risks for hereditary prostate cancer.
Prostate cancer occurs frequently in the general population, with the average man’s lifetime risk of developing prostate cancer being approximately 11.6% (SEERP). Although the majority of prostate cancer cases are not related to heritable factors, in approximately 5-10% cases the disease is caused by a specific genetic change (Carter et al, 1992). Men who carry these genetic changes may be at significantly increased risk of developing prostate cancer in their lifetime. For instance, carriers of pathogenic mutations in EPCAM, MLH1, MSH2, MSH6, and PMS2 have a 2 to 3 fold increased risk for prostate cancer compared to the general population, and carriers of HOXB13 mutations have a 30-60% lifetime risk (Karlsson et al, 2014; Macinnis et al, 2013). Frequently, changes in genes that result in increased risks for prostate cancer also predispose individuals to increased risks for other malignancies.
This panel includes genes associated with:
- Lynch syndrome (hereditary non-polyposis colon cancer)
- Hereditary breast and ovarian cancer syndrome (HBOC)
- Li-Fraumeni syndrome
Hereditary prostate cancer is typically inherited in an autosomal dominant manner, although several of the genes on this panel are associated with recessive genetic conditions:
- MLH1, MSH2, PMS2, and MSH6 are associated with constitutional mismatch repair deficiency
- ATM is associated with ataxia telangiectasia
- BRCA2 is associated with Fanconi anemia
- NBN is associated with Nijmegen breakage syndrome
Indications for Testing
- A personal history of prostate cancer
- A personal history of multiple primary cancers
- A family history suggestive of a hereditary cancer syndrome, including multiple individuals on the same side of a family diagnosed with cancer, especially at ages below population averages
- Risk assessment for asymptomatic family of members of proband with molecular diagnosis of a hereditary cancer syndrome
Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent flanking bases, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of a single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering.
Included Genes (13)
Additions to the Prostate Cancer Panel:
Emerging evidence genes can also be added onto the comprehensive panel. These genes do not have a clear association with hereditary prostate cancer, but emerging evidence suggests that they may play a role in disease pathogenesis.
Emerging Evidence (1):
- Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC. Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci USA. 1992;89(8):3367-71.
- Karlsson R, Aly M, Clements M, et al. A population-based assessment of germline HOXB13 G84E mutation and prostate cancer risk. Eur Urol. 2014;65(1):169-76.
- Macinnis RJ, Severi G, Baglietto L, et al. Population-based estimate of prostate cancer risk for carriers of the HOXB13 missense mutation G84E. PLoS ONE. 2013;8(2):e54727.
- Surveillance, Epidemiology, and End Results Program (SEERP). Cancer Stat Fact Sheets [Accessed April 20, 2017]. Available from: http://seer.cancer.gov/