M TP53
Chronic lymphocytic leukemia/small lymphocytic lymphoma, acute myeloid leukemia, multiple myeloma, solid tumors
Next Generation Sequencing (NGS) on the Illumina MiSeqDX
10 days
5.0 mL (min 3.0 mL) peripheral blood or (min 2.0 mL) bone marrow in EDTA, Sodium Heparin or ACD
Ship at ambient temperature, cool in summer. (Do not allow cool/refrigerated pack to directly contact sample.)
Improper specimen labeling; Incorrect specimen; Clotted specimen; Specimen older than 7 days.
TP53 mutation analysis is a qualitative test providing full coding sequence coverage of TP53. The National Comprehensive Cancer Network recommends TP53 mutation testing prior to therapy initiation in patients with CLL/SLL (National Comprehensive Cancer Network, 2019). Ibrutinib is an FDA-approved BTK inhibitor for CLL patients with mutations that alter TP53 function (Farooqui, et al., 2015; National Comprehensive Cancer Network, 2019; Amin, Balasubramanian, Saiya-Cork, & Malek, 2015). In CLL as in virtually all other cancer types TP53 mutations are associated with more aggressive tumors and poor overall outcome (Robles, Jen, & Harris, 2016; Zenz, et al., 2010; Le Bris, et al., 2017).
Amin, N. A., Balasubramanian, S., Saiya-Cork, K., & Malek, S. N. (2015). Mutations and Other Cell-Intrinsic Determinants of the Apoptotic Response to Ibrutinib in Chronic Lymphocytic Leukemia. Blood, 126, 4165. Retrieved from http://www.bloodjournal.org/content/126/23/4165.abstract
Farooqui, M. Z., Valdez, J., Martyr, S., Aue, G., Saba, N., Niemann, C. U., . . . Stetler-Stevenson, M. (2015). Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. The Lancet. Oncology, 16, 169-176. doi:10.1016/S1470-2045(14)71182-9
Le Bris, Y., Struski, S., Guièze, R., Rouvellat, C., Prade, N., Troussard, X., . . . Ysebaert, L. (2017). Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia. Hematological Oncology, 35, 664-670. doi:10.1002/hon.2349
National Comprehensive Cancer Network. (2019). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 5.2019-May 23, 2019.
Robles, A. I., Jen, J., & Harris, C. C. (2016). Clinical Outcomes of TP53 Mutations in Cancers. Cold Spring Harbor perspectives in medicine, 6, a026294. doi:10.1101/cshperspect.a026294
Zenz, T., Eichhorst, B., Busch, R., Denzel, T., Häbe, S., Winkler, D., . . . Stilgenbauer, S. (2010). TP53 Mutation and Survival in Chronic Lymphocytic Leukemia. Journal of Clinical Oncology, 28, 4473-4479. doi:10.1200/JCO.2009.27.8762