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TP53

From www.haematologyetc.co.uk


Gene affected: TP53 - the name relates to its molecular mass initially detected by protein electrophoresis: 53kDa


Clinical significance Mutation is relatively infrequent generally in AML (and has uncertain significance), however incidence of mutated p53 protein increases in treatment related AML so may play a role in treatment resistance. It is seen particularly in complex karyotype AML where it is recognised to mediate adverse outcome. Mutation occurs also in CML and in MDS (associated with adverse outcome).



Function of gene

TP53 is a key tumor suppressor protein involved in maintenance of genomic stability, including regulation of cellular senescence, apoptosis, metabolism, and DNA repair. In hematopoietic stem cells p53 regulates the quiescence and self-renewal.


NGS panel gene coverage

Exons 2-11




Occurrence:


AML
Despite the importance of TP53 to cancer in general, and the importance in particular lymphoid malignancies, mutation of TP53 is surprisingly uncommon in the context of de-novo AML (about 8%).
Mutation is however frequent in complex-karyotype AML (70%) (generally older with low counts and often an erythroid type).
Mutation of TP53 has been shown to be an independent adverse factor for outcome; and is also frequent in treatment-related AML (30%).
Other myeloid disorders
TP53 mutation is an initiating driver mutation in some cases of MDS where it is reported to mediate adverse outcome, and is seen also in both chronic phase and blast crisis of CML.

Associated genetic features:

Appears mutually exclusive with other frequently mutated genes (NPM1, FLT3, MDM2, ARF and DNMT3A mutation).


Links


GeneWiki link:
Gene Wiki entry for TP53


References
1. TP53 mutation in AML
2. TP53 mutation in CML
3. Prognosis in MDS (1)
4. Prognosis in MDS (2)