This test analyzes the APC gene. Pathogenic variants in this gene can cause APC-associated polyposis conditions, which include familial adenomatous polyposis (FAP) and three FAP subtypes: attenuated FAP (AFAP), Gardner syndrome, and Turcot syndrome. These disorders are primarily associated with the development of numerous colon polyps and colon cancer.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
APC can also be ordered as part of a broader panel to test for different types of hereditary cancer, including colorectal and pancreatic cancers. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.
Familial adenomatous polyposis (FAP) is a colorectal cancer syndrome characterized by the development of hundreds to thousands of precancerous (adenomatous) polyps, typically beginning in adolescence or early adulthood. Without a prophylactic colectomy, individuals with FAP have a lifetime risk of almost 100% of developing colorectal cancer. One specific pathognomonic finding is congenital hyperplasia of the retinal pigment epithelium (CHRPE), which requires a specialized eye examination to identify.
FAP has three subtypes: Gardner syndrome, Turcot syndrome, and attenuated FAP (AFAP). Gardner syndrome has the same disease progression and risk of colon cancer as classic FAP but is also associated with the development of other extracolonic findings, both benign and malignant. These include desmoid tumors, sebaceous cysts, osteomas, supernumerary teeth, and cancer of the duodenum, exocrine pancreas, thyroid (papillary adenocarcinoma), liver (hepatoblastomas), and central nervous system (medulloblastomas). Turcot syndrome presents with numerous colon adenomas and medulloblastomas.AFAP has a later age of onset than classic FAP, presents with fewer adenomatous polyps (<100), and has an overall lower lifetime risk of developing cancer (approximately 70%).
FAP is a highly penetrant condition. If it is left untreated, affected individuals have a lifetime risk of nearly 100% of developing colorectal cancer. For AFAP, the lifetime risk for colorectal cancer is 70%. See the table below for specific cancer risks:
|Cancer type||Cancer risk|
|Colon||Up to 100% (70% for attenuated FAP)|
|Hepatoblastoma (up to age 5)||1%-2%|
|Gastric||Up to 0.5%|
Analysis of the APC gene detects pathogenic variants in up to 90% of individuals with clinical FAP.
FAP is inherited in an autosomal dominant pattern. Most cases are inherited from a parent; however, up to 25% of cases are due to a spontaneous de novo mutation.
APC-associated polyposis conditions historically accounted for approximately 0.5% of all colorectal cancer, but this number is decreasing with increased awareness, early detection, and intervention. Collectively, the APC-associated polyposis conditions have a prevalence of approximately 2-3 in 100,000 individuals.
A clinical diagnosis of FAP is established if an individual has at least one of the following:
A clinical diagnosis of attenuated FAP (AFAP) should be considered if an individual has at least one of the following:
For additional details, see the clinical criteria for FAP and AFAP established by the National Comprehensive Cancer Network:
For management recommendations, please refer to:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|
APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.