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)

Highlights

This test is complementary to fluorescence in situ hybridization (FISH) analysis for the 17p- abnormality but more appropriately identifies the presence of variant alteration and gene inactivation in tumor cells.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
CSP53 TP53 Pre-Analysis Cell Sorting, V No No

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.

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

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR) and Sanger Sequencing

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

TP53 gene somatic mutation analysis

Aliases
Lists additional common names for a test, as an aid in searching

TP53

P53

CLL

BCLL

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.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

For the evaluation of patients suspected of having an inherited or germline TP53 cancer syndrome (eg, Li Fraumeni syndrome), order TP53Z / TP53 Gene, Li Fraumeni Syndrome, Full Gene Analysis, Varies.

Shipping Instructions

Blood and bone marrow specimens must arrive within 10 days of collection.

Necessary Information

The following information is required:

1. Pertinent clinical history

2. Clinical or morphologic suspicion

3. Date of collection

4. Specimen source

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Submit only 1 of the following specimens:

 

Specimen Type: Blood (preferred)

Container/Tube: Lavender top (EDTA) or yellow top (ACD solution B)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

3. Label specimen as blood.

Specimen Stability Information: Ambient/Refrigerate <10 days

 

Specimen Type: Bone marrow

Container/Tube: Lavender top (EDTA), yellow top (ACD solution B), or green top (heparin)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix bone marrow.

2. Send specimen in original tube.

3. Label specimen as bone marrow.

Specimen Stability Information: Ambient/Refrigerate <10 days

 

Specimen Type: Tissue

Container/Tube: Plastic container

Specimen Volume: 100 mg

Collection Instructions: Stabilize fresh tissue in tissue culture medium or freeze immediately after collection.

Specimen Stability Information: Refrigerate 24 hours/ Frozen

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

Forms

1. Molecular Hematopathology Patient Information: B-Cell Chronic Lymphocytic Leukemia (CLL) for IGVH and/or TP53 Somatic Mutation Testing in Special Instructions

2. If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood, bone marrow: 1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Extracted DNA Reject
Moderately to severely clotted Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred) 10 days

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

Method Description
Describes how the test is performed and provides a method-specific reference

Peripheral blood specimens from chronic lymphocytic leukemia (CLL) patients only will be analyzed by a screening flow cytometry method to determine B-cell content and confirm the presence of a clonal B-cell population. Blood samples (but not bone marrows) from patients with CLL are enriched for B-lymphocytes by cell sorting and DNA is extracted from the B-cell fraction. For other sample types (bone marrow, fresh or frozen tissues) DNA is extracted directly without prior enrichment. Polymerase chain reaction (PCR) and Sanger sequencing of TP53 exons 4 to 9 is performed. Sequence analysis is performed using Mutation Surveyor and Alamut software. The presence of a detected variant is then assessed using curated public databases of known TP53 gene mutations.(The TP53 Web Site entry UMD TP53 Mutation Database. Accessed 12/3/2013; den Dunnen JT, Antonarakis SE: Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat. 2000;15:7-12)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

7 to 14 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

DNA 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81352-TP53 (tumor protein 53) (eg, tumor samples), full gene sequence or targeted sequence analysis of >5 exons

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports