Test Catalog

Test ID: P53CA    
Hematologic Neoplasms, TP53 Somatic Mutation, DNA Sequencing Exons 4-9, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluating chronic lymphocytic leukemia patients at diagnosis or during disease course for the presence of TP53 gene variants indicating high risk of disease progression and adverse outcomes


This test is not intended for the evaluation of patients suspected of having an inherited or germline TP53 cancer syndrome (eg, Li Fraumeni syndrome)

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Flow cytometry will be performed on peripheral blood samples to verify diagnosis of chronic lymphocytic leukemia (CLL) and to selectively enrich for B-cells in samples with a clonal population.


See TP53 Sequencing Testing Algorithm in Special Instructions.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Patients with chronic lymphocytic leukemia (CLL) have variable disease course influenced by a series of tumor biologic factors. The presence of chromosomal 17p- or a TP53 gene variant confers a very poor prognosis to a subset of CLL patients, both at time of initial diagnosis, as well as at disease progression, or in the setting of therapeutic resistance. TP53 gene variant status in CLL has emerged as the single most predictive tumor genetic abnormality associated with adverse outcome and poor response to standard immunochemotherapy; however, patients can be managed with alternative therapeutic options.


Although the prognostic relevance of an acquired TP53 gene variant is best studied for CLL, similar findings are also reported for other hematologic malignancies including low-grade B-cell lymphoma, diffuse large B-cell lymphoma, and some types of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Therefore, while this test has been developed to be primarily focused on high-risk CLL patients, TP53 gene sequencing analysis can also be performed in additional neoplasms, as clinically indicated.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Genetic variants present or absent as compared to a reference sequence of the normal TP53 gene

Interpretation Provides information to assist in interpretation of the test results

Results are reported in standard nomenclature according to the most recent Human Genome Variation Society (HGVS) recommendations and an interpretive comment regarding the nature of the sequence variant (eg, known deleterious, suspected deleterious, synonymous change) will be included to complete the clinical report.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test will not detect all possible acquired variants in the TP53 gene because it is restricted to analyzing exons 4 to 9. However, this region encompasses more than 90% of described pathologic variants and covers the coding exons of the critical DNA binding regions.


The analytical sensitivity of the assay can be affected by the absolute B-cell number in the peripheral blood or tissue sample, as well as the often subclonal nature of this tumor genetic abnormality. The assay attempts to compensate in part for this by performing an initial screening flow cytometry to assess B-cell quantity and by performing the cell enrichment step (for the peripheral blood specimens only) to isolate relatively pure CD19+ B-cells for analysis. Nevertheless, the nature of the Sanger sequencing method is such that typical reproducible analytic sensitivity will be in the order of 25% variant allele burden.


Because optimal cell enrichment is dependent on the absolute B-cell quantity, samples with a very low WBC or initial percentage of B cells (determined from flow cytometry or WBC automated cell count) will likely result in poor assay performance and inability to detect possible TP53 gene variants in the tumor population.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Zenz T, Krober A, Scherer K, et al: Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood. 2008;112:3322-3329

2. Lehmann S, Oqawa S, Raynaud SD, et al: Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia. Cancer. 2008;112:1296-1305

3. Rossi D, Cerri M, Deambrogi C, et al: The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness. Clin Cancer Res. 2009;15(3):995-1004

4. Zent CS, Call TG, Hogan WJ, et al: Update on risk-stratified management for chronic lymphocytic leukemia. Leuk Lymphoma. 2006;47(9):1738-1746

5. Trbusek M, Smardova J, Malcikova J, et al: Missense mutations located in structural p53 DNA-binding motifs are associated with extremely poor survival in chronic lymphocytic leukemia. J Clin Oncol. 2011;29:2703-2708

6. Halldorsdottir AM, Lundin A, Murray F, et al: Impact of TP53 mutation and 17p deletion in mantle cell lymphoma. Leukemia. 2011;25:1904-1908

7. Young KH, Leroy K, Moller MB, et al: Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study. Blood. 2008;112:3088-3098

Special Instructions Library of PDFs including pertinent information and forms related to the test