Test Code: 2197

Prostate cancer: Sequencing Panel
Test Code: 2197
Turnaround time: 7 weeks

CONDITION DESCRIPTION
Prostate cancer is the second leading cause of cancer related death in men, with a lifetime risk of 1:7 (1,2). The incidence of prostate cancer varies worldwide with Asian men typically having a very low incidence, with age-adjusted incidence rates ranging from 2 to 10 cases per 100,000 men (3). Higher incidence rates are typically noted in northern European countries, but with the highest incidence among African American men; the latter being 60% higher incidence rate than Caucasian men (4).

An estimated range from 5% to 10% of prostate cancer cases are primarily caused by high-risk inherited genetic factors or prostate cancer susceptibility genes. This risk is greater for men with affected brothers when compared with men who have affected fathers (5). In addition, the risk is increased when a first-degree relative is diagnosed with prostate cancer before age 65 years (5,6). Prostate cancer risk may also increase in men who have a family history of breast/ovarian cancer and BRCA1/BRCA2 mutations (7,8,9). Germline mutations in HOXB13 (10), as well as mutations in Lynch syndrome (11) also increase prostate-cancer risk.

References:
1. American Cancer Society: Cancer Facts and Figures 2015. Atlanta, Ga: American Cancer Society, 2015.
2. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer.
3. Stanford JL, Stephenson RA, Coyle LM, et al., eds.: Prostate Cancer Trends 1973-1995. Bethesda, Md: National Cancer Institute, 1999. NIH Pub. No. 99-4543.
4. Miller BA, Kolonel LN, Bernstein L, et al., eds.: Racial/Ethnic Patterns of Cancer in the United States 1988-1992. Bethesda, Md: National Cancer Institute, 1996. NIH Pub. No. 96-4104.
5. Kiciński M, Vangronsveld J, Nawrot TS: An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis. PLoS One 6 (10): e27130, 2011.
6. Kalish LA, McDougal WS, McKinlay JB: Family history and the risk of prostate cancer. Urology 56 (5): 803-6, 2000.
7. Gayther SA, de Foy KA, Harrington P, et al.: The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators. Cancer Res 60 (16): 4513-8, 2000.
8. Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators. Cancer Res 60 (16): 4513-8, 2000.
9. Agalliu I, Karlins E, Kwon EM, et al.: Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer. Br J Cancer 97 (6): 826-31, 2007.
10. Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, Wiley KE, Isaacs SD, Johng D, Wang Y, Bizon C, Yan G, Gielzak M, Partin AW, Shanmugam V, Izatt T, Sinari S, Craig DW, Zheng SL, Walsh PC, Montie JE, Xu J, Carpten JD, Isaacs WB, Cooney KA. Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med. 2012 Jan 12;366(2):141-9.
11. Haraldsdottir S, Hampel H, Wei L, Wu C, Frankel W, Bekaii-Saab T, de la Chapelle A, Goldberg RM. Prostate cancer incidence in males with Lynch syndrome. Genet Med. 2014 Jul;16(7):553-7.

GENES
BRCA1, BRCA2, CHEK2, NBN, and TP53

INDICATIONS
The test is indicated for:

  • Individuals with a clinical or suspected diagnosis of Prostate cancer.

METHODOLOGY
Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

DETECTION
Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.
Analytical Sensitivity: ~99%.

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types
* Preferred specimen type: Whole Blood

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) tube:
Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml.

Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Isolated DNA
Specimen Requirements:
In microtainer: 60 μg.
Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.

RELATED TESTS

  • CEN4GEN Prostate cancer: Extended Sequencing Panel