Mutations of the p53 gene

The p53 gene is the most commonly mutated gene in cancer but p53 abnormalities are much less common in hematologi-cal malignancies. As in solid tumors, mutations tend to occur in exons 5-8 of the p53 gene. They are found principally in RAEB, RAEB-T and in CMML. Interestingly, they generally occur in association with a deletion of the other allele. It is possible that this may represent an example in MDS of Knudson's hypothesis, whereby the two hits are: (1) a deletion of one chromosome 17, and (2) a p53 mutation on the partner chromosome. The cases harboring p53 mutations generally have complex karyotypic abnormalities, making it difficult to assess the contribution of the p53 abnormalities to the leukemia.

These p53 mutations are associated with the pseudo-Pel-ger-Huet anomaly and vacuoles in neutrophils giving rise to the 17p- syndrome, one of the rare phenotype-genotype associations reported in MDS (the principal one being the 5q- syndrome; see below).

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