Prostate Cancer Panel

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesCPT Code Copy CPT Codes
5459 ATM 81408,81479 Add to Order
BRCA1 and BRCA2 81162
BRIP1 81479,81479
CHEK2 81479,81479
EPCAM 81479,81403
HOXB13 81479,81479
MLH1 81292,81294
MSH2 81295,81297
MSH6 81298,81300
NBN 81479,81479
PALB2 81406,81479
PMS2 81317,81319
RAD51C 81479,81479
RAD51D 81479,81479
TP53 81405,81479
Full Panel Price* $540
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
5459 Genes x (16) $540 81162, 81292, 81294, 81295, 81297, 81298, 81300, 81317, 81319, 81403, 81405, 81406, 81408, 81479(x16) Add to Order

Pricing Comments

We are happy to accommodate requests for single genes or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available.

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

The great majority of tests are completed within 20 days.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Prostate cancer is the most frequently diagnosed cancer in males in the United States (Siegel et al. 2017. PubMed ID: 28055103). A man’s lifetime risk of developing invasive prostate cancer is 1 in 8 (Siegel et al. 2017. PubMed ID: 28055103). This disorder is typically considered a cancer of the elderly, and the median age of onset is ~68 years. However, recent studies suggest an increase in the incidence of early onset of prostate cancer (Gupta et al. 2017. PubMed ID: 28413383). Initially prostate cancer may be asymptomatic, but more advanced prostate cancers usually cause symptoms, which include problems urinating, blood in the urine, trouble getting an erection, and pain in the hips, spine and chest (American Cancer Society. 2014). When prostate cancer is limited to the prostate gland itself, it may be curable. However, cancer cells may spread to other parts of the body, particularly the lymph nodes and bones (American Cancer Society. 2014). Early diagnosis is critical to successful treatment.

Genetics

Prostate cancer is highly heritable, with an overall estimated heritability of 40% - 60% (Lichtenstein et al. 2000. PubMed ID: 10891514; Hjelmborg et al. 2014. PubMed ID: 24812039). Approximately 5% -10% of prostate cancer is caused by rare pathogenic variants in susceptibility genes (Steinberg et al. 1990. PubMed ID: 2251225; Carter et al. 1992. PubMed ID: 1565627; Pritchard et al. 2016. PubMed ID: 27433846). The mode of inheritance appears to be autosomal dominant (AD) (Schaid et al. 1998. PubMed ID: 9585590).

This prostate cancer next generation sequencing panel assesses genes that have been shown to be causative when mutated for disorders that have prostate cancer as a clinical feature.

ATM: Ataxia-telangiectasia is an autosomal recessive disorder caused by pathogenic variants in the ATM gene. ATM encodes a serine protein kinase (ATM) that is involved in DNA repair via phosphorylation of downstream proteins. It senses double-strand DNA breaks, coordinates cell-cycle checkpoints prior to repair, and recruits repair proteins to damaged DNA sites (Taylor et al. 2004. PubMed ID: 15279810). Pathogenic variants in ATM result in defective checkpoint cycling. Previous studies suggest an association between ATM heterozygous carriers and prostate cancer susceptibility. For example, a retrospective case series of patients with prostate cancer found that 1.6% (11 of 692) had an ATM pathogenic variant (Pritchard et al. 2016. PubMed ID: 27433846). Specific variants, such as ATM p.Ser49Cys, have been found to be associated with an increased risk of prostate cancer (Dombernowsky et al. 2008. PubMed ID: 18565893).

BRCA1 and BRCA2: BRCA1 is a tumor suppressor gene that is involved in a number of cellular processes including DNA damage repair, cell cycle progression, gene transcription and ubiquitination. BRCA2 is a tumor suppressor gene that along with RAD51 has a large role in DNA repair processes and genome stability. Male carriers of BRCA1 and BRCA2 pathogenic variants have a higher risk of developing cancers, including prostate cancer (Thompson and Easton. 2002. PubMed ID: 12237281; Liede et al. 2004. PubMed ID: 14966099). Particularly, prostate cancer has been observed at higher rates in BRCA2 carriers than in the general population (Mersch et al. 2015. PubMed ID: 25224030).

CHEK2: CHEK2 encodes a protein kinase that protects the genome from ionizing radiation and genotoxic insults. To date, approximately 90 pathogenic variants have been reported throughout the CHEK2 gene, and >90% are detectable by sequencing (Human Gene Mutation Database). It has been suggested that CHEK2 may be a potential prostate cancer susceptibility gene (Wang et al. 2015. PubMed ID: 26629066).

HOXB13: HOXB13 is involved in embryonic development and regulation of androgen receptor target genes. It is a tumor suppressor, and germline variants have been associated with prostate cancer susceptibility with an odds ratio of 3-8 (Zhen et al. 2018. PubMed ID: 29669169).

MLH1, MSH2, MSH6, PMS2, and EPCAM: Germline pathogenic variants in these genes have been associated with Lynch syndrome. Previous studies have suggested that prostate cancer may be observed in patients harboring a mismatch repair (MMR) gene pathogenic variant (Grindedal et al. 2009. PubMed ID: 19723918; Haraldsdottir et al. 2014. PubMed ID: 24434690: Rosty et al. 2014. PubMed ID: 25117503).

NBN: Nijmegen breakage syndrome (NBS) has been associated with an elevated risk of prostate cancer (Cybulski et al. 2013. PubMed ID: 23149842; Cybulski et al. 2004. PubMed ID: 14973119). The NBN protein normally associates with the MRE11A and RAD50 proteins to form the MRN complex. The MRN complex, upon DNA damage, is involved in DNA repair and cell cycle arrest via the ATM kinase. Pathogenic variants in NBN lead to faulty DNA repair and improper cell cycle control. In Eastern European with NBS, c.657_661del5 is the most common pathogenic variant and accounts for more than 90% of all mutant alleles in NBN (Varon et al. 1998. PubMed ID: 9590180).

TP53: Li-Fraumeni syndrome (LFS) is inherited in an autosomal dominant manner and is caused by heterozygous germline pathogenic variants in the TP53 gene (Malkin et al. 1990. PubMed ID: 1978757; Srivastava et al. 1990. PubMed ID: 2259385). TP53 encodes the often studied cellular tumor p53 antigen (Soussi. 2010. PubMed ID: 20930848). p53 is a ubiquitously expressed DNA-binding protein that plays a major role in the regulation of cell division, DNA repair, programmed cell death, and metabolism. More than 200 pathogenic variants have been reported throughout the TP53 gene, and nearly all are detectable by DNA sequencing (Human Gene Mutation Database). Several gross deletions encompassing one or more exons of the TP53 gene have been described (Human Gene Mutation Database), but these account for less than 1% of all LFS patients (Schneider et al. 2013. PubMed ID: 20301488). The average risk of developing cancer for carriers of TP53 pathogenic variants has been estimated to be ~73% for men (Chompret et al. 2000. PubMed ID: 10864200). In a Dutch case series of 180 families with Li-Fraumeni syndrome or Li-Fraumeni-like syndrome, a TP53 pathogenic variant was identified in 24 families (Ruijs et al. 2010. PubMed ID: 20522432). Li-Fraumeni syndrome is responsible for multiple cancers including prostate cancer. In a French case series of 214 families with TP53 pathogenic variants, 4 prostate cancer cases were reported (Bougeard et al. 2015. PubMed ID: 26014290).

A few other genes such as PALB2, RAD51C and RAD51D are included in this NGS panel based on preliminary evidence of their involvement in prostate cancer (Pritchard et al. 2016. PubMed ID: 27433846).

Testing Strategy

For this Next Generation Sequencing (NGS) test, sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization kit, followed by massively parallel sequencing of the captured DNA fragments.

For Sanger sequencing, polymerase chain reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Copy number variants (CNVs) are also detected from NGS data. We utilize a CNV calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution and zygosity of any variants within each target region are used to reinforce CNV calls. All CNVs are confirmed using another technology such as aCGH, MLPA, or PCR before they are reported.

This panel typically provides ≥98% coverage of all coding exons of the genes listed, plus ~10 bases of flanking noncoding DNA. We define coverage as ≥20X NGS reads or Sanger sequencing.

This test also includes analysis of the inversion of exons 1-7 in MSH2.

Clinical Sensitivity - Sequencing and CNV

This panel analyzes genes that have been associated with hereditary prostate cancer. It is difficult to estimate the clinical sensitivity of this test due to the paucity of large cohort studies. However, in a recent study of 692 men with documented metastatic prostate cancer, pathogenic variants in these genes were identified: ATM (11 pathogenic variants [1.6%l]), BRCA1 (6 [0.9%]), BRCA2 (37 [5.3%]), CHEK2 (10 [1.9%]), and PALB2 (3 [0.4%]) (Pritchard et al. 2016. PubMed ID: 27433846).

Indications for Test

This test is suitable for individuals with a personal and/or family history of prostate cancer. Individuals with or without a family history of prostate cancer with early onset (<50 years) should be assessed with this panel. This test especially aids in a differential diagnosis of similar phenotypes, rules out particular syndromes, and provides analysis of multiple genes simultaneously. This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.

Genes

Official Gene Symbol OMIM ID
ATM 607585
BRCA1 113705
BRCA2 600185
BRIP1 605882
CHEK2 604373
EPCAM 185535
HOXB13 604607
MLH1 120436
MSH2 609309
MSH6 600678
NBN 602667
PALB2 610355
PMS2 600259
RAD51C 602774
RAD51D 602954
TP53 191170
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • American Cancer Society- www.cancer.org.
  • Bougeard et al. 2015. PubMed ID: 26014290
  • Carter et al. 1992. PubMed ID: 1565627
  • Chompret et al. 2000. PubMed ID: 10864200
  • Cybulski et al. 2004. PubMed ID: 14973119
  • Cybulski et al. 2013. PubMed ID: 23149842
  • Dombernowsky et al. 2008. PubMed ID: 18565893
  • Grindedal et al. 2009. PubMed ID: 19723918
  • Gupta et al. 2017. PubMed ID: 28413383
  • Haraldsdottir et al. 2014. PubMed ID: 24434690
  • Hjelmborg et al. 2014. PubMed ID: 24812039
  • Human Gene Mutation Database (Bio-base).
  • Lichtenstein et al. 2000. PubMed ID: 10891514
  • Liede et al. 2004. PubMed ID: 14966099
  • Malkin et al. 1990. PubMed ID: 1978757
  • Mersch et al. 2015. PubMed ID: 25224030
  • Pritchard et al. 2016. PubMed ID: 27433846
  • Rosty et al. 2014. PubMed ID: 25117503
  • Ruijs et al. 2010. PubMed ID: 20522432
  • Schaid et al. 1998. PubMed ID: 9585590
  • Schneider et al. 2013. PubMed ID: 20301488
  • Siegel et al. 2017. PubMed ID: 28055103
  • Soussi. 2010. PubMed ID: 20930848
  • Srivastava et al. 1990. PubMed ID: 2259385
  • Steinberg et al. 1990. PubMed ID: 2251225
  • Taylor et al. 2004. PubMed ID: 15279810
  • Thompson and Easton. 2002. PubMed ID: 12237281
  • Varon et al. 1998. PubMed ID: 9590180
  • Wang et al. 2015. PubMed ID: 26629066
  • Zhen et al. 2018. PubMed ID: 29669169

Ordering/Specimens

Ordering Options

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.

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.

Specimen Types

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