Familial Adenomatous Polyposis (FAP) Mutation Screen
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Confirmation of familial adenomatous polyposis (FAP) diagnosis for patients with clinical features
This test should be ordered only for individuals with symptoms suggestive of FAP. Asymptomatic patients with a family history of FAP should not be tested until a mutation has been identified in an affected family member.
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
APC gene sequence analysis for exons 1-14 and PTT for exon 15. Changes identified in exon 15 via PTT are verified by DNA sequencing. Gene dosage analysis by multiplex ligation probe amplification (MLPA) is used to investigate for the presence of large deletions and duplications encompassing the coding regions as well as promoter 1A and 1B of the APC gene.
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
See Colonic Adenomatous Polyposis Syndromes Testing Algorithm in Special Instructions.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis/Protein Truncation Test with Follow-up sequencing when appropriate
Gene Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)
Direct Mutation Analysis Utilizing Fluorescent DNA Sequencing
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
FAP Mutation Screen
Adenomatous Polyposis Coli (APC)
APC (Adenomatous Polyposis Coli)
APC (Adenomatous Polyposis Coli)
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Specimen must arrive within 96 hours of draw.
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
1. Invert several times to mix blood.
2. Send specimen in original tube.
1. Molecular Genetics-Inherited Cancer Syndromes Patient Information Sheet (Supply T519) in Special Instructions
2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
3. If not ordering electronically, submit a Molecular Genetics Request Form (Supply T245) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
No specimen should be rejected. If specimen not received at appropriate temperature or in wrong anticoagulant, include note to laboratory. If questions, contact laboratory.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by mutations in the APC gene located on the long arm of chromosome 5 (5q21). Classic FAP is characterized by progressive development of hundreds to thousands of adenomatous colon polyps. Polyps may develop during the first decade of life and the majority of untreated FAP patients will develop colon cancer by age 40. Typically, there is a predominance of polyps on the left side of the colon, however other areas of the colon my also be affected. The presence of extracolonic manifestations is variable and includes gastric and duodenal polyps, ampullary polyps, osteomas, dental abnormalities (unerupted teeth), congenital hypertrophy of the retinal pigment epithelium (CHRPE), benign cutaneous lesions, desmoids tumors, hepatoblastoma, and extracolonic cancers. Common constellations of colonic and extracolonic manifestations have resulted in the designation of 3 clinical variants: Gardner syndrome, Turcot syndrome, and hereditary desmoid disease.
Gardner syndrome is characterized by colonic polyps of classic FAP with epidermoid skin cysts and benign osteoid tumors of the mandible and long bones. Turcot syndrome is characterized by multiple colonic polyps and central nervous system (CNS) tumors.
Turcot syndrome is an unusual clinical variant of FAP, as it is also considered a clinical variant of hereditary nonpolyposis colorectal cancer (HNPCC). Individuals with Turcot syndrome have CNS tumors in addition to adenomatous polyps. The types of CNS tumor observed helps to distinguish Turcot-FAP variant patients from Turcot-HNPCC variant patients. The predominant CNS tumor associated with the Turcot-FAP variant is medulloblastoma, while glioblastoma is the predominant CNS tumor associated with Turcot-HNPCC.
Hereditary desmoid disease (HDD) is a variant of FAP with multiple desmoids tumors as the predominant feature. Many patients with HDD may not even show colonic manifestations of FAP. APC germline testing may assist clinicians in distinguishing a sporadic desmoid tumor, from that associated with FAP.
Attenuated FAP (AFAP) is characterized by later onset of disease and a milder phenotype (typically <100 adenomatous polyps and fewer extracolonic manifestations) than classic FAP. Typically individuals with AFAP develop symptoms of the disease at least 10 to 20 years later than classically affected individuals. Individuals with AFAP often lack a family history of colon cancer and/or multiple adenomatous polyps. Of note, clinical overlap is observed between AFAP and MYH-associated polyposis (MAP), an autosomal recessive polyposis syndrome typically associated with fewer than 100 polyps. Although the clinical phenotype of MAP remains somewhat undefined, extracolonic manifestations, including CHRPE have been described in affected patients. Given the phenotypic overlap of AFAP and MAP, these tests are commonly ordered together or in a reflex fashion.
See Colorectal Adenomatous Polyposis Algorithm in Special Instructions for additional information. Also see Hereditary Colorectal Cancer: Adenomatous Polyposis Syndromes (September 2004 Communique') in publications for additional information.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A small percentage of individuals who are carriers or have a diagnosis of FAP may have a mutation that is not identified by this method (eg, promoter mutations, deep intronic alterations). The absence of a mutation(s), therefore, does not eliminate the possibility of positive carrier status or the diagnosis of FAP. For carrier testing, it is important to first document the presence of an APC gene mutation in an affected family member.
In some cases, DNA alterations of undetermined significance may be identified.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
In addition to disease-related probes, the multiplex ligation probe amplification (MLPA) technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. American Society of Clinical Oncology. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility Clin Oncol. 2003;21:2397-2406
2. Half E, Bercovich D, Rozen P: Familial adenomatous polyposis. Orphanet J Rare Dis. 2009 Oct 12;4:22
3. Croner RS, Brueckl WM, Reingruber B, et al: Age and manifestation related symptoms in familial adenomatous polyposis. BMC Cancer 2005 Mar 2;5:24
Method Description Describes how the test is performed and provides a method-specific reference
DNA sequencing is used to detect mutations in exons 1-14 (segment 1) and the 5' end of exon 15. The protein truncation test is used to screen for mutations in exon 15 (segments 2-5) of the APC gene. If an alteration is detected within exon 15, DNA sequencing will be performed to characterize the alteration. MLPA is used to detect large deletions/duplications encompassing the coding and non-coding regions as well as promoter 1A and 1B of the APC gene.
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Thursday; 10 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Whole Blood: 2 weeks (if available) Extracted DNA: 3 months
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81201-APC (adenomatous polyposis coli) (eg, familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; full gene sequence
81203-APC (adenomatous polyposis coli) (eg, familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; duplication/deletion variants
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|17262||Reason For Referral||42349-1|