• Test Code:
    1442
  • Department:
  • Test Synonyms:
    APC full gene sequencingFamilial Adenomatous Polyposis (FAP) sequencing
  • CPT Code(s):
    81201
Background:

Familial adenomatous polyposis (FAP) is an autosomal dominant cancer syndrome caused largely by mutations in APC, and to a lesser degree, MUTYH. FAP patients develop hundreds of colorectal adenomas at a young age (often in the teenage years), as well as extracolonic polyps, cutaneous lesions, desmoids tumors, osteomas, and dental abnormalities, with an average age of diagnosis of 34.5-43 years. An attenuated form of FAP (AFAP) is similar to FAP, with a decidedly less severe phenotype (less than 100 adenomas), and diagnosed approximately 12 years later than an FAP patient. Other colorectal cancer syndromes have also been associated with mutations in APC such as Gardner syndrome and Turcot syndrome, which have slightly different phenotypes than FAP. Depending on the population studied, small germline mutations in APC account for 70-90% of FAP cases and 16% of AFAP cases while larger deletions and duplications of APC account for approximately 15% of FAP/AFAP cases. Mutations of MUTYH also account for approximately 30% of patients with an AFAP phenotype and 7-30% of patients with a FAP phenotype. While APC mutations manifest in an autosomal dominant manner, most patients with MUTYH defects have biallelic mutations. However there may be other genetic and environmental factors that play a role in the FAP/AFAP phenotypes.

Reasons for Referral:

  • Identification of inherited genetic defects in APC in patients with FAP/AFAP characteristics or early onset colon cancer
  • Confirmation of a suspected diagnosis with a positive family history of early onset colon cancer when a familial mutation is known
  • Predispositional testing for asymptomatic family members with a positive family history of colorectal cancer

Methodology:

Sequencing for APC is carried out by amplification of all exons and intron/exon boundaries followed by bi-directional Sanger sequencing. The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions. All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity. Sequencing and deletion/duplication analysis of FAP/AFAP genes may be analyzed individually or as a panel.

Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B):

    • Adult: 5mL
    • Child: 5mL
    • Infant: 2-3mL

Saliva: 2 ORAgene Saliva Kit(s) (OGR-500)

DNA: 10µg at a minimum of 100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

14 - 21 days

Shipment Sensitivity Requirements:

Package and ship specimen to remain cold, but not frozen.  Ship via overnight express, using the FedEx priority overnight label provided.  Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

  1. Aretz S, et al. Large submicroscopic genomic APC deletions are a common cause of typical familial adenomatous polyposis. J Med Genet 2005; 42: 185-192.
  2. Giardiello F, et al. AGA Technical Review on Hereditary Colorectal Cancer and Genetic Testing. Gastroenterology 2001; 121: 198-213.
  3. Nielsen M, et al. Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis. Clin Genet 2007; 71: 427-433.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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