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  • Test code: 01362
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Prostate Cancer Panel

Test description

This test analyzes up to 17 genes associated with a hereditary predisposition to prostate cancer. These genes were selected based on available evidence to provide Invitae’s most comprehensive test targeting hereditary prostate cancer.

Genetic testing may confirm a clinical diagnosis and guide treatment and management decisions. At-risk relatives may also be identified, allowing pursuit of a diagnostic evaluation, early detection and improved clinical outcome. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (12 genes)

ATM BRCA1 BRCA2 CHEK2 EPCAM HOXB13 MLH1 MSH2 MSH6 NBN PMS2 TP53

Add-on Preliminary-evidence Genes for Prostate Cancer (5 genes)

In addition to the primary panel, clinicians can also choose to include genes that have limited evidence of association with hereditary prostate cancer. At this time, the association of these genes with hereditary prostate cancer remains uncertain; however, some clinicians may wish to include genes that may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

BRIP1 FANCA PALB2 RAD51C RAD51D

  • hereditary breast and ovarian cancer syndrome (HBOC)
  • Li-Fraumeni syndrome (LFS)
  • Lynch syndrome – also known as hereditary non-polyposis colorectal cancer (HNPCC)

Prostate cancer is the fifth-most-common malignancy in the world. A man’s lifetime risk for developing this type of cancer is 1 in 7 (15%). More than 60% of cases are diagnosed after age 65; it is rarely found in individuals under 40.

Prostate cancer is currently considered to be a complex, multifactorial disease, with the vast majority of familial clustering attributed to the interaction of multiple shared susceptibility genes and environmental factors.

Inherited pathogenic variants in certain genes—particularly ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PMS2, and TP53—account for some cases of hereditary prostate cancer. Men with pathogenic variants in these genes have an increased risk of developing prostate cancer and, in some cases, other cancers as well.

Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant may manifest with different symptoms, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may be beneficial. For gene-associated cancer risks, see the table below.

GeneProstate cancer riskReferences (PMIDs)
ATM elevated 26000489, 27433846, 24556621
BRCA1 ~20% 14966099, 23747895
BRCA2 ~20% 10433620, 16141007
CHEK2 elevated 15492928, 25431674, 23149842
EPCAM up to 30% 23530095, 24425144
HOXB13 up to 60% 23457453, 25595936, 22841674
MLH1 up to 30% 23530095, 24425144
MSH2 up to 30% 23530095, 24425144
MSH6 up to 30% 23530095, 24425144
NBN elevated 23149842, 14973119
PMS2 up to 30% 23530095, 24425144
TP53 unknown 20301488

Elevated: There is evidence of association, but the penetrance and risk are not well characterized.
Unknown: Based on small studies, the risk may possibly be increased, but it is not well described.

The genes on this panel confer an increased risk of developing prostate cancer in an autosomal dominant inheritance pattern. Several of these genes also result in clinically-distinct autosomal recessive conditions, as outlined below:

  • BRCA2 is associated with Fanconi anemia
  • MLH1, MSH2, PMS2, and MSH6 are associated with constitutional mismatch repair deficiency (CMMR-D)
  • ATM is associated with ataxia telangiectasia (A-T)
  • NBN is associated with Nijmegen breakage syndrome (NBS)

This panel may be considered for individuals with prostate cancer. Other candidates for testing include those whose history is suggestive of a hereditary cancer syndrome, such as a personal and/or family history of:

  • prostate, breast, ovarian, uterine, colon, pancreatic, melanoma, or sarcoma, particularly if early onset (<50)
  • prostate cancer with a Gleason score ≥7
  • metastatic or high to very high risk localized prostate cancer
  • male breast cancer
  • breast or ovarian cancer and Ashkenazi Jewish ancestry

There are also some common, general features suggestive of a hereditary cancer syndrome family. These include:

  • cancer diagnosed at an unusually young age
  • different types of cancer that have occurred independently in the same person
  • cancer that has developed in both organs of a set of paired organs (e.g., both kidneys; both breasts)
  • several close blood relatives that have the same type of cancer
  • unusual cases of a specific cancer type (e.g., breast cancer in a man)

  1. Breast, Cancer, Linkage, Consortium. Cancer risks in BRCA2 mutation carriers. J. Natl. Cancer Inst. 1999; 91(15):1310-6. doi: 10.1093/jnci/91.15.1310. PMID: 10433620
  2. Liede, A, et al. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J. Clin. Oncol. 2004; 22(4):735-42. PMID: 14966099
  3. Cybulski, C, et al. NBS1 is a prostate cancer susceptibility gene. Cancer Res. 2004; 64(4):1215-9. doi: 10.1158/0008-5472.can-03-2502. PMID: 14973119
  4. Cybulski, C, et al. CHEK2 is a multiorgan cancer susceptibility gene. Am. J. Hum. Genet. 2004; 75(6):1131-5. PMID: 15492928
  5. van, Asperen, CJ, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J. Med. Genet. 2005; 42(9):711-9. PMID: 16141007
  6. Schneider, K, et al. Li-Fraumeni Syndrome. 1999 Jan 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle. PMID: 20301488
  7. Karlsson, R, et al. A population-based assessment of germline HOXB13 G84E mutation and prostate cancer risk. Eur. Urol. 2014; 65(1):169-76. PMID: 22841674
  8. Stott-Miller, M, et al. HOXB13 mutations in a population-based, case-control study of prostate cancer. Prostate. 2013; 73(6):634-41. PMID: 23129385
  9. Cybulski, C, et al. An inherited NBN mutation is associated with poor prognosis prostate cancer. Br. J. Cancer. 2013; 108(2):461-8. doi: 10.1038/bjc.2012.486. PMID: 23149842
  10. MacInnis, RJ, et al. Population-based estimate of prostate cancer risk for carriers of the HOXB13 missense mutation G84E. PLoS ONE. 2013; 8(2):e54727. PMID: 23457453
  11. Raymond, VM, et al. Elevated risk of prostate cancer among men with Lynch syndrome. J. Clin. Oncol. 2013; 31(14):1713-8. PMID: 23530095
  12. Li, D, et al. The role of BRCA1 and BRCA2 in prostate cancer. Front Biosci (Landmark Ed). 2013; 18:1445-59. PMID: 23747895
  13. Ryan, S, et al. Risk of prostate cancer in Lynch syndrome: a systematic review and meta-analysis. Cancer Epidemiol. Biomarkers Prev. 2014; 23(3):437-49. PMID: 24425144
  14. Hale, V, et al. CHEK2 (∗) 1100delC Mutation and Risk of Prostate Cancer. Prostate Cancer. 2014; 2014:294575. PMID: 25431674
  15. Kote-Jarai, Z, et al. Prevalence of the HOXB13 G84E germline mutation in British men and correlation with prostate cancer risk, tumour characteristics and clinical outcomes. Ann. Oncol. 2015; 26(4):756-61. PMID: 25595936
  16. National Comprehensive Cancer Network®, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Breast and Ovarian. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed January 2018.
  17. National Library of Medicine Genetics Home Reference. Prostate cancer. http://ghr.nlm.nih.gov/condition/prostate-cancer. Accessed January 2018.
  18. U.S. Department of Health and Human Services. What is Your Prostate? http://archive.ahrq.gov/patients-consumers/prevention/understanding/bodysys/edbody13.html, Accessed January 2018.
  19. Robson, ME, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J. Clin. Oncol. 2010; 28(5):893-901. PMID: 20065170
  20. Gronwald, J, et al. Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of mutation type and cancer site in proband. Br. J. Cancer. 2009; 100(9):1508-12. PMID: 19401704
  21. Olsen, JH, et al. Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia. Br. J. Cancer. 2005; 93(2):260-5. PMID: 15942625
  22. Thompson, D, et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J. Natl. Cancer Inst. 2005; 97(11):813-22. doi: 10.1093/jnci/dji141. PMID: 15928302
  23. Olivier, M, et al. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res. 2003; 63(20):6643-50. PMID: 14583457
  24. Na, R, et al. Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death. Eur. Urol. 2017; 71(5):740-747. PMID: 27989354
  25. van, Os, NJ, et al. Health risks for ataxia-telangiectasia mutated heterozygotes: A systematic review, Meta-analysis and evidence-based guideline. Clin. Genet. 2015; :None. PMID: 26662178
  26. Pritchard, CC. et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. NEJM, 2016 PMID: 27433846
  27. Cheng, HH, et al. A Pilot Study of Clinical Targeted Next Generation Sequencing for Prostate Cancer: Consequences for Treatment and Genetic Counseling. Prostate. 2016; 76(14):1303-1311. PMID: 27324988
  28. Moran, A, et al. Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam. Cancer. 2012; 11(2):235-42. PMID: 22187320
  29. Cai, Q, et al. Germline HOXB13 p.Gly84Glu mutation and cancer susceptibility: a pooled analysis of 25 epidemiological studies with 145,257 participates. Oncotarget. 2015; 6(39):42312-21. PMID: 26517352
  30. Beebe-Dimmer, JL, et al. The HOXB13 G84E Mutation Is Associated with an Increased Risk for Prostate Cancer and Other Malignancies. Cancer Epidemiol. Biomarkers Prev. 2015; 24(9):1366-72. PMID: 26108461
  31. Hoffmann, TJ, et al. Imputation of the rare HOXB13 G84E mutation and cancer risk in a large population-based cohort. PLoS Genet. 2015; 11(1):e1004930. PMID: 25629170
  32. Xu, J, et al. HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG). Hum. Genet. 2013; 132(1):5-14. PMID: 23064873
  33. Ewing, CM, et al. Germline mutations in HOXB13 and prostate-cancer risk. N. Engl. J. Med. 2012; 366(2):141-9. PMID: 22236224
  34. Huang, H, Cai, B. G84E mutation in HOXB13 is firmly associated with prostate cancer risk: a meta-analysis. Tumour Biol. 2014; 35(2):1177-82. PMID: 24026887
  35. Steffen, J, et al. Increased cancer risk of heterozygotes with NBS1 germline mutations in Poland. Int. J. Cancer. 2004; 111(1):67-71. doi: 10.1002/ijc.20239. PMID: 15185344
  36. di, Masi, A, Antoccia, A. NBS1 Heterozygosity and Cancer Risk. Curr. Genomics. 2008; 9(4):275-81. doi: 10.2174/138920208784533610. PMID: 19452044
  37. Pakkanen, S, et al. PALB2 variants in hereditary and unselected Finnish prostate cancer cases. J Negat Results Biomed. 2009; 8:12. PMID: 20003494
  38. Tischkowitz, M, et al. Analysis of the gene coding for the BRCA2-interacting protein PALB2 in hereditary prostate cancer. Prostate. 2008; 68(6):675-8. PMID: 18288683
  39. Erkko, H, et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature. 2007; 446(7133):316-9. PMID: 17287723
  40. Pelttari, LM, et al. A Finnish founder mutation in RAD51D: analysis in breast, ovarian, prostate, and colorectal cancer. J. Med. Genet. 2012; 49(7):429-32. PMID: 22652533
  41. Wilkes, DC, et al. A germline FANCA alteration that is associated with increased sensitivity to DNA damaging agents. Cold Spring Harb Mol Case Stud. 2017; 3(5):None. PMID: 28864460
  42. Hayano, T, et al. Germline Variants of Prostate Cancer in Japanese Families. PLoS ONE. 2016; 11(10):e0164233. PMID: 27701467
  43. Beltran, H, et al. Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response. JAMA Oncol. 2015; 1(4):466-74. PMID: 26181256
  44. Giri, VN, et al. Inherited Mutations in Men Undergoing Multigene Panel Testing for Prostate Cancer: Emerging Implications for Personalized Prostate Cancer Genetic Evaluation. JCO Precision Oncology, 2017
  45. National Comprehensive Cancer Network®, Clinical practice guidelines in oncology. Prostate Cancer. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed February 2018.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ATM NM_000051.3
BRCA1* NM_007294.3
BRCA2* NM_000059.3
BRIP1 NM_032043.2
CHEK2 NM_007194.3
EPCAM* NM_002354.2
FANCA NM_000135.2
HOXB13* NM_006361.5
MLH1* NM_000249.3
MSH2* NM_000251.2
MSH6 NM_000179.2
NBN NM_002485.4
PALB2 NM_024675.3
PMS2 NM_000535.5
RAD51C NM_058216.2
RAD51D NM_002878.3
TP53* NM_000546.5

BRCA1: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
EPCAM: Analysis is limited to deletion/duplication analysis.
HOXB13: Analysis is limited to the NM_006361.5:c.251G>A, p.Gly84Glu variant.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
TP53: Deletion/duplication analysis covers the promoter region.