26480 Hematologic Neoplasms, TP53 Somatic Mutation, DNA Sequencing Exons 4-9, Varies (P53CA)

​​​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)

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

Submit only 1 specimen type per order.

Blood or Bone Marrow Collection Instructions:
Invert several times to mix blood or bone marrow.
Send blood or bone marrow specimen in original tube.  DO NOT aliquot.
Label specimen clearly as blood or bone marrow.​

Tissue Collection Instructions:
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.

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 and acute myeloid leukemia. 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.

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

​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.