The AXIN2 gene is associated with autosomal dominant oligodontia-colorectal cancer syndrome (MedGen UID: 324868).
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The AXIN2 gene encodes an inhibitor of the Wnt signaling pathway, a regulator of gene transcription. Dysregulation of this pathway is known to contribute to cancer progression.
MedGen UID: 324868
Oligodontia, defined as the congenital agenesis of six or more permanent teeth, is relatively rare. It can occur in isolation but is most often associated with other congenital anomalies. The AXIN2 gene is essential for the development of permanent teeth; pathogenic variants in this gene are known to cause oligodontia and features of ectodermal dysplasia including sparse eyebrows, scalp, and body hair. Recent evidence has also found that individuals with such variants in AXIN2 are also predisposed to developing adult-onset colon adenomas, polyps, and colorectal cancer. This condition is called oligodontia-colorectal cancer syndrome. Affected individuals may present with oligodontia and/or colorectal cancer (the risks for each is currently unclear because the number of reported cases is limited [PMID: 15042511, 21416598, 26025668]). An individual with an AXIN2 pathogenic variant may not necessarily develop cancer in their lifetime, but their risk for cancer is increased over the general population risk.
The AXIN2 gene codes for the Axin-related protein, Axin2, and presumably plays an important role in the regulation of the stability of beta-catenin in the Wnt signaling pathway. Degradation of beta-catenin appears to be an important event in the genesis of a number of malignancies (Gene ID: 8313. http://www.ncbi.nlm.nih.gov/gene/8313. Accessed February 2018). If there is a pathogenic variant in this gene that prevents it from functioning normally, there is an increased risk to develop certain types of cancers.
Oligodontia-colorectal cancer syndrome due to pathogenic variants in the AXIN2 gene has autosomal dominant inheritance. This means that an individual with a pathogenic variant has a 50% chance of passing the condition on to their offspring. Once a pathogenic mutation is detected in an individual, it is possible to identify at-risk relatives who can pursue testing for this specific familial variant. While many cases are inherited from a parent, some occur spontaneously. Many cases are inherited from a parent, but some cases can occur spontaneously (i.e., an individual with a pathogenic variant has parents who do not have it). An individual with a variant in AXIN2 has a 50% risk of passing that variant on to offspring.
Management guidelines for individuals with pathogenic AXIN2 variants have been developed. The National Comprehensive Cancer Network® (NCCN®) suggests the following (NCCN. Genetic/Familial High-Risk Assessment: Colorectal. Version 3.2017):
Data regarding pathogenic AXIN2 variants and their associated colorectal risks are currently limited, but information regarding hereditary cancer susceptibility genes is constantly increasing. Clinically relevant AXIN2 data are likely to become available in the near future. Knowing if a pathogenic AXIN2 variant is present is advantageous: At-risk relatives can be identified, enabling pursuit of a diagnostic evaluation. Awareness of this cancer predisposition also encourages patients and their providers to inform at-risk family members, to diligently follow standard screening protocols, and to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information.
Referenced with permission from the NCCN Genetic/Familial High-Risk Assessment: Colorectal. Version 3.2017. © National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed February 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.
The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a statement of consensus of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Review date: February 2018
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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|