TP53, P53,CLL, BCLL
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)
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.
Blood and bone marrow specimens must arrive within 10 days of collection.
The following information is required:
1. Pertinent clinical history
2. Clinical or morphologic suspicion
3. Date of collection
4. Specimen source
Stabilize fresh tissue in tissue culture medium or freeze immediately after collection.
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.
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.