TP53 (17p13) / CEP17 Del

TP53 is also the most frequently mutated gene in human cancer with a mutation frequency of up to 90% in solid tumors and an average of 10% alterations in hematologic malignancies. TP53 deletions are often associated with mutations of the second allele, supporting the “two-hit” hypothesis of cancer development. If both mutation and deletion of TP53 are present, there is a significant negative impact on overall survival in hematological malignancies. In multiple myeloma, 33.8% of newly diagnosed patients carry a TP53 deletion, with even higher frequencies at relapse (54.5%). In acute myeloid leukemia (AML), 13% of patients show TP53 alterations, including 5% with mutations and deletions and 1% with deletion only. Patients with myelodysplastic neoplasms (MDS) show TP53 alterations in 7% of the cases, including 1% with mutations and deletions and 1% with deletion only. In AML and MDS, TP53 alterations and 17p deletion are associated with a complex karyotype, poor response to therapy, and reduced survival. In MDS, even TP53 deletion without mutation of the second allele has a significant negative impact on overall survival.