TP53 Mutations in Myelodysplastic Syndrome

Abstract

Mutations of the TP53 tumor suppressor gene, contributing to the development and progression of a wide variety of human malignancies, are found in some of the patients with myelodysplastic syndromes (MDS). Previous reports revealed that TP53 mutations were found in 0-25% of patients with MDS and are closely associated with a complex abnormal karyotype including such chromosomal losses as -5/5q-, -7/7q- and/or 17p-, which are known to be frequent in therapy-related leukemias. We have also detected TP53 mutation in 10 (14%) of 70 patients with MDS. All of the mutations were detected at the time of diagnosis, which suggest the TP53 mutation may play a role in the development of MDS. Those patients with a TP53 mutation had a poor prognosis regardless of leukemic transformation or not.

The reported mutational spectra of TP53 in MDS and ANLL differ from those of colon and lung cancers. Compared with other hematological disorders, the spectrum of TP53 mutations in MDS and ANLL is assumed to be associated with pathogenic exposure to known or unknown carcinogens, as suggested by the chromosomal findings. Further studies are required to clarify the pathogenesis of this heterogenous disease entity.

Key Words:

• myelodysplastic syndrome
• p53 gene
• karyotype
• NRAS gene
• molecular epidemiology