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APC genetic testing

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  • A person with 10 or more adenomatous colorectal polyps (cumulative count) before 30 yrs of age
  • A person with 20 or more adenomatous colorectal polyps (cumulative count) regardless of age
  • Persons 10-60 yrs of age with an intra-abdominal or abdominal wall desmoid tumour
  • A person who has a relative in whom a pathogenic APC mutation has been identified

Genetic testing is essential for good clinical care of individuals who are suspected of having a heritable mutation in this gene.

The results of the following investigations may significantly influence the likelihood of detecting a heritable mutation in the APC gene: 

  • the cumulative number of adenomatous colorectal polyps
  • where multiple colorectal adenomas are documented in an isolated family member (i.e. apparently sporadic adenomatous polyposis) consider also testing for homozygous recessive mutations in MUTYH
  • where multiple colorectal adenomas are documented in 2 or more full-sibs in the absence of a family history consider testing for homozygous recessive mutations in MUTYH
  • detection of a somatic mutation in the CTNNB1 (beta-catenin) gene in a desmoid tumour (available evidence indicates somatic CTNNB1 and germline APC mutations are mutually exclusive).

The frequency of APC germline mutations in unselected individuals with CRC is <0.2%.r

Over 70% of patients with a typical FAP phenotype have an APC mutation identified.

Of patients with an attenuated FAP phenotype, 30% have an APC mutation identified (and of the APC negatives, 57% may have  MUTYH mutations).r

About 15-20% of APC mutations arise de novo.

Factors Probability of detecting a heritable mutation
More than 100 adenomatous polyps 60-93%rr
Between 20 and 100 adenomatous polyps 30%r
Extra colonic manifestations (when colorectal polyp status is unknown)  
  • multiple osteomas of the skull or mandible

Unknown
  • intra-abdominal or abdominal wall desmoid tumour diagnosed at 10-60 yrs age

7.5r-16%r
  • desmoid tumour (any location) diagnosed <10 yrs age

Unknown
  • multiple and/or bilateral CHRPE at any age

Unknown
Patient has a first or second degree relative with documented pathogenic mutation 25-50%

 Abbreviation: CHRPE - congenital hypertrophy of the retinal pigment epithelium

Evidence of mismatch repair deficiency within colorectal carcinoma or polyp.

Colorectal polyposis due to non-adenomatous polyps (e.g. serrated, hamartomatous, juvenile etc).

Colorectal polyposis due to polyps of mixed histology (e.g. significant numbers of both serrated and adenomatous polyps).

Person with isolated, single CHRPE (congenital hypertrophy of the retinal pigment epithelium) after review by an ophthalmologist.

Predictive testing should never be ordered when only an unclassified variant or polymorphism has been identified in a family.

A range of testing methodologies are needed to identify pathogenic changes in the APC gene including:

  • sequencing
  • copy number analysis (e.g. MLPA)

Information about DNA tests and testing laboratories is available from:

If a decision is made to test this gene(s) as part of a cancer gene panel, care should be taken to select a panel where the individual genes tested have both clinical validity and clinical utility.

Result Reference databases Considerations and advice
Mutation search
Pathogenic mutation InSiGHT APC (Familial adenomatous polyposis) - risk management
Variant   Review periodically
Identify other genes for which a mutation search could be considered
Inconclusive   Identify other genes for which a mutation search could be considered
Predictive testing
Family mutation identified   APC (Familial adenomatous polyposis) - risk management
Family mutation not found   Screening tailored based on a revised risk estimate

Centre for Genetics Education NSW Health
Hereditary Cancer Registry
InSight
EuroGene Test
Clinical Molecular Genetics Society Best Practice Guidelines

Further references

For further references used to develop this protocol please see the History icon.

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Version 5

Date Summary of changes
13/08/2010 Published
05/09/2011 Reviewed at September reference committee meeting no changes to document.
02/04/2014

Discussed at August 2012 reference committee meeting, review continued via email and the following changes made:

  • Placed into new format.
  • Target population - updated.
  • Investigations which should be considered before germline genetic testing - updated.
  • Factors which influence the pre-test probability of a heritable mutation including table - updated.
  • Circumstances in which testing is not indicated - updated.
  • Diagnostic testing - Link to Human Genetics Society of Australasia removed as per discussion at March 5 2014 reference committee meeting.
  • Websites - updated.
  • References - updated.
  • Review second yearly.
30/09/2015 Sentence added to Genetic Testing protocol template: if a decision is made to test this gene(s) as part of a cancer gene panel, care should be taken to select a panel where the individual genes tested have both clinical validity and clinical utility.
20/02/2017

Protocol reviewed at the October 2016 RC meeting and the following changes made:

  • Target population - wording updated
  • Investigations which should be considered - updated
  • Factors which influence the pre-test probability of a heritable - updated
  • Diagnostic testing - updated to new format
  • References - updated
  • Changed to version 3
  • Next review in 2 years. 
31/05/2017 Transferred to new eviQ website. Version number changed to V.4.
01/06/2018
  • 'Gene Tests' link in Testing Methods section relabelled as GeneReviews.
  • Removed link to the Clinical molecular genetics society best practice guidelines in Result Interpretation section, as webpage no longer available.
 

 Further references used to develop this protocol:

Trainer, A. H. 2009. "Extra-colonic manifestations of familial adenomatous polyposis coli." Adv Exp Med Biol 656:119-127.
28/08/2019 Protocol title changed from 'Genetic testing for heritable mutations in the APC gene' to 'APC genetic testing' in accordance with Cancer Genetics Reference Committees' consensus. Version number increased to V.5.

The information contained in this document is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to care or treatment. Any clinician seeking to apply or consult this document is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/746

30 May 2020