Colorectal Cancer Predisposition via the POLE Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7511 POLE 81479 81479,81479 $540 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7511POLE81479 81479 $540 Order Options and Pricing

Pricing Comments

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.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Colorectal cancer (CRC) is the development of tumors in the colon and rectum that occur in approximately 8% of individuals with cancer (Siegel et al. 2015). Similar to other cancers, CRC is caused by genetic and environmental factors (e.g. smoking, diet). Approximately 30% of CRCs are considered familial and 5% of CRCs are caused by a Mendelian disorder (Esteban-Jurado 2014). Colorectal cancer is generally broken down into the presence or absence of polyposis (numerous internal polyps). CRC inherited diseases include Lynch syndrome, Familial Adenomatous polyposis, Peutz-Jeghers, Juvenile Polyposis and Cowden syndrome. A recent syndrome has been coined CRC-polymerase proofreading-associated polyposis (PPAP). It is caused by pathogenic variants in proofreading DNA repair genes (Palles et al. 2012). Mutations in these genes predispose individuals to adenomatous polyposis or early-onset cancer (Spier et al. 2015). Identification of pathogenic variants in the germline of CRC patients is important for cancer surveillance (i.e. colonoscopy) for the affected individual and family members, since early surveillance and treatment has been shown to decrease morbidity and mortality (Kohlmann and Gruber 2014).

Genetics

Colorectal predisposition syndrome is inherited in an autosomal dominant manner. Polymerase proof-reading-associated polyposis (PPAP) is caused by pathogenic variants in two proofreading DNA repair genes POLD1 and POLE (Chubb et al. 2015). The protein products of these genes are involved in the replication of DNA and are also involved in DNA repair. POLE catalyzes the synthesis of the leading strand, while POLD catalyzes synthesis of Okazaki fragments of the lagging strand. (Church et al. 2013). Mutations in the proof-reading exonuclease domains of these proteins result in the inability to correct mismatched bases during DNA replication. Pathogenic variants in the POLE gene result in predisposition to colorectal cancer (Church et al. 2013). Tumors from individuals with these pathogenic variants are microsatellite stable, but acquire base substitution mutations (Palles et al. 2012). Reported pathogenic variants in POLE include missense variants and small deletions (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the POLE gene have been observed in 0.3-0.6% of individuals with colorectal cancer (Chubb et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the POLE gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

This test is suitable for individuals with multifocal, recurrent, and early onset (e.g. < 50 years) colorectal and endometrial tumors or a family history of these tumors. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

Gene

Official Gene Symbol OMIM ID
POLE 174762
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Colorectal cancer, susceptibility to, 12 AD 615083

Citations

  • Chubb D, Broderick P, Frampton M, Kinnersley B, Sherborne A, Penegar S, Lloyd A, Ma YP, Dobbins SE, Houlston RS. 2015. Genetic Diagnosis of High-Penetrance Susceptibility for Colorectal Cancer (CRC) Is Achievable for a High Proportion of Familial CRC by Exome Sequencing. Journal of Clinical Oncology 33: 426–432. PubMed ID: 25559809
  • Church DN, Briggs SEW, Palles C, Domingo E, Kearsey SJ, Grimes JM, Gorman M, Martin L, Howarth KM, Hodgson SV, The NSECG Collaborators, Kaur K, Taylor J, Tomlinson IP. 2013. DNA polymerase and exonuclease domain mutations in endometrial cancer. Human Molecular Genetics 22: 2820–2828. PubMed ID: 23528559
  • Esteban-Jurado C. 2014. New genes emerging for colorectal cancer predisposition. World Journal of Gastroenterology 20: 1961. PubMed ID: 24587672
  • Human Gene Mutation Database (Bio-base).
  • Kohlmann W, Gruber SB. 2014. Lynch Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301390
  • Palles C, Cazier J-B, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Almeida EG, Salguero I, Sherborne A, Chubb D, Carvajal-Carmona LG, Ma Y, Kaur K, Dobbins S, Barclay E, Gorman M, Martin L, Kovac MB, Humphray S; CORGI Consortium; WGS500 Consortium, Lucassen A, Holmes CC, Bentley D, Donnelly P, Taylor J, Petridis C, Roylance R, Sawyer EJ, Kerr DJ, Clark S, Grimes J, Kearsey SE, Thomas HJ, McVean G, Houlston RS, Tomlinson I. 2012. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nature Genetics 45: 136–144. PubMed ID: 23263490
  • Siegel RL, Miller KD, Jemal A. 2015. Cancer statistics, 2015: Cancer Statistics, 2015. CA: A Cancer Journal for Clinicians 65: 5–29. PubMed ID: 25559415
  • Spier I, Holzapfel S, Altmüller J, Zhao B, Horpaopan S, Vogt S, Chen S, Morak M, Raeder S, Kayser K, Stienen D, Adam R, Nürnberg P, Plotz G, Holinski-Feder E, Lifton RP, Thiele H, Hoffmann P, Steinke V, Aretz S. 2015. Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas: POLE Mutations in Polyposis. International Journal of Cancer n/a–n/a. PubMed ID: 25529843

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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