This test analyzes CEBPA, a gene that is associated with familial acute myeloid leukemia (AML) syndrome. This condition is an autosomal dominant myelodysplastic/acute leukemia predisposition syndrome that is highly penetrant for the development of AML. Age of onset is variable but reportedly in the range of early childhood through late adulthood.
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.
If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, though deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Sample requirements page for more details.
These genes can also be ordered as part of broader panels. Depending on the individual’s clinical and family history, one of these panels may be appropriate and can be ordered at no additional charge.
Familial acute myeloid leukemia (AML) with mutated CEBPA is a hematologic malignancy predisposition syndrome that is characterized by isolated AML in the presence of a family history of AML. This condition has near-complete penetrance: Carriers of a pathogenic variant develop AML at some point in their lifetime. Age of onset is variable, even within the same family; some affected individuals present in early childhood and others in adulthood.
Germline mutations in CEBPA may be found in combination with a somatic mutation. An estimated 7%–11% of individuals with AML who have an acquired CEBPA mutation detected by tumor profiling of leukemic cells, will have familial AML with biallelic mutations in CEBPA.
Individuals who carry a germline pathogenic variant in CEBPA have a high risk of developing acute leukemia.
Familial acute myeloid leukemia with mutated CEBPA is inherited in an autosomal dominant pattern.
The prevalence of familial AML with mutated CEBPA is unknown.
Testing for germline CEBPA mutations is recommended for:
If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type that is not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, though deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Sample requirements page for more details.
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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
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|