TP53 encodes a tumor suppressor protein that normally responds to diverse cellular stresses to induce cell cycle arrest, apoptosis, senescence, DNA repair or changes in metabolism. Somatic, loss of function mutations in TP53 are one of the most frequent in cancer and result in loss of the anti-proliferative and tumor suppressive effects of the p53 protein. In some malignancies, such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), TP53 mutations are associated with an adverse prognosis resulting in the use of more aggressive treatment. Somatic mutations can also be associated with age-related clonal hematopoiesis in the absence of an overt hematologic malignancy. Germline TP53 mutations are associated with Li-Fraumeni Syndrome – a familial predisposition to a variety of malignancies including sarcomas, breast carcinoma, gliomas and adrenocortical carcinomas.
This DNA test is performed by targeted next-generation sequencing (NGS) and will detect mutations within the sequenced regions of TP53 exons 2 - 11 (NM_000546.5). See the table below for the specific regions sequenced by this assay. The reference genome assembly used for alignment and variant calling is hg19 (GRCh37).
Interpretive Report Provided
*Reference ranges may change over time. Please refer to the original patient report when evaluating results.
This test will only detect mutations within specific gene regions sequenced (see University of Michigan Pathology Handbook for specific information). This test may fail to detect mutations below the limit of detection of this assay (approximately 5% variant allele frequency; 10% neoplastic cells for a heterozygous mutation). This test does not detect gene/exon-level copy number alterations and may not detect large insertion/deletion mutations (> 200 bp). Variant allele frequencies are approximations and may be affected by the percentage of neoplastic cells within the sample, subclonal molecular alterations, concomitant copy number alterations, etc. This test cannot definitively distinguish between somatic and germline variants. Additional testing may be required if there is concern for a clinically relevant germline alteration. The clinical implications of the findings in this report may change based on evolution of the scientific literature. Misinterpretation of results may occur if clinicopathologic information provided is inaccurate or incomplete.
Collect blood or bone marrow in a lavender top tube. Refrigerate and send intact blood or bone marrow specimen within 48 hours of collection. Fresh tissue (preferably 0.5 cm3, sent in RPMI) and fresh aspirates or body fluids are acceptable. Refrigerate and send, preferably within 24 hours. Frozen tissue specimens – preferably frozen with 1 hour of collection – may also be sent frozen on dry ice. Fresh cell suspensions in RPMI should be refrigerated and sent, preferably within 48 hours. Frozen cell suspensions – preferably frozen with 1 hour of collection – may also be sent frozen on dry ice. Fixed cytogenetic cell suspensions or pellets in Carnoy’s fixative. Refrigerate and send. For formalin-fixed, paraffin-embedded tissue, a block containing an area with a high percentage of neoplastic cells is preferred. Unstained, UNBAKED slides (5-8, 10-micron slides; 10-15 if few neoplastic cells are present) with associated H&E stained slide are also acceptable. Decalcified tissue or other fixatives will be accepted and the assay attempted; however, these may result in failed testing due to degraded nucleic acid. Both blocks and slides should be stored at room temperature.
Fibroblast culture from skin biopsy or buccal swab may be acceptable for additional testing intended to differentiate germline and somatic molecular alterations.
By ordering this test the clinician acknowledges that informed consent has been obtained from the patient as required by applicable state or federal laws and the ordering clinician has authorization from the patient permitting MLabs to report the test results to the ordering clinician. Test includes microdissection billed as a separate additional charge. Test includes pathologist interpretation of results billed as a separate additional charge. This test is not available without interpretation.