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TP53
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Interpretation 2278
Tier 1
TP53
Variants
TP53 any mutation
Primary Sites
Blood
Bone Marrow
Tumor Types
Acute Myeloid Leukemia
Myeloproliferative Neoplasm
Mast Cell Neoplasm
Primary Myelofibrosis
Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Chronic Myeloid Leukemia
Chronic Neutrophilic Leukemia
Cytopenia
Eosinophilia
Essential Thrombocythemia
Histiocytic and Dendritic Cell Neoplasms
Langerhans Cell Histiocytosis
Leukocytosis
Leukopenia
MDS with Ring Sideroblasts
Monocytosis
Myelodysplastic/Myeloproliferative Neoplasm
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
T Lymphoblastic Leukemia/Lymphoma
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

TP53 encodes p53, a tumor suppressor protein that consists of transactivation domain, proline-rich domain, DNA-binding domain, oligomerization domain, and regulatory domain. p53 responds to diverse cellular stresses to maintain genomic stability and to induce cell cycle arrest, apoptosis, DNA repair and metabolic changes. TP53 mutations represent an important mechanism of resistance to DNA-damaging chemotherapeutic agents. Somatic TP53 mutations are found in a variety of cancers with various frequencies depending on cancer type; overall, TP53 is mutated in over one-half of human cancers. Missense mutations were the most frequent (~70-80%), followed by frameshift and nonsense mutations. Most TP53 mutations are clustered in the DNA-binding domain encompassing exons 5 and 8. These mutations either directly disrupt the DNA-binding domain of TP53 or cause conformational changes of the TP53 protein, thus leading to severely impaired TP53 function. Overall in myeloid malignancies, TP53 mutations are found in 5% to 15% of de novo MDS and AML but 20% of myelodysplastic syndrome with isolated del(5q) and ~50% of MDS/AML with complex karyotype. TP53 mutations are also more frequent in therapy-associated myeloid neoplasm (21-38%) compared to de novo MDS and AML. TP53 mutations are also found in 8% of blastic plasmacytoid dendritic cell neoplasm, and less than 5% in myeloproliferative neoplasms (ET, PV and PMF) and chronic myelomonocytic leukemia. TP53 mutations are independently associated with a poor prognosis in myelodysplastic syndrome (NCCN Guidelines for Myelodysplastic Syndromes) and is a poor risk factor in AML (NCCN Guildelines for AML). TP53 mutations are also associated with resistance to lenalidomide or relapse during lenalidomide treatment. TP53 mutations are independently associated with unfavorable outcomes and shorter survival after hematopoietic stem cell transplantation in patients with myelodysplastic syndrome and myelodysplastic syndrome/acute myeloid leukemia, but an increased response to decitabine in patients with myelodysplastic syndrome or acute myeloid leukemia.

Citations
  1. Bowen D, et al. TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis. Leukemia 2009;23(1):203-6
  2. Ok CY, et al. TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases. J Hematol Oncol 2015;8():45
  3. Kadia TM, et al. TP53 mutations in newly diagnosed acute myeloid leukemia: Clinicomolecular characteristics, response to therapy, and outcomes. Cancer 2016;122(22):3484-3491
  4. Zhang L, et al. The role of p53 in myelodysplastic syndromes and acute myeloid leukemia: molecular aspects and clinical implications. Leuk Lymphoma 2017;58(8):1777-1790
  5. Kim MP, et al. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer. Front Oncol 2015;5():249
  6. Jadersten M, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol 2011;29(15):1971-9
  7. Menezes J, et al. Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Leukemia 2014;28(4):823-9
  8. Ozaki R, et al. A new tool to detect kidney disease in Chinese type 2 diabetes patients: comparison of EZSCAN with standard screening methods. Diabetes Technol Ther 2011;13(9):937-43
  9. Jadersten M, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol 2011;29(15):1971-9
  10. Metzeler KH, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128(5):686-98
  11. Menezes J, et al. Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Leukemia 2014;28(4):823-9
  12. Raza S, et al. TP53 mutations and polymorphisms in primary myelofibrosis. Am J Hematol 2012;87(2):204-6
  13. Itzykson R, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol 2013;31(19):2428-36
  14. Tefferi A, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv 2016;1(1):21-30
  15. Metzeler KH, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128(5):686-98
  16. Della Porta MG, et al. Clinical Effects of Driver Somatic Mutations on the Outcomes of Patients With Myelodysplastic Syndromes Treated With Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol 2016;34(30):3627-3637
  17. Welch JS, et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. N Engl J Med 2016;375(21):2023-2036
  18. Jadersten M, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol 2011;29(15):1971-9
Last updated: 2020-07-24 14:50:01 UTC
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