Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies

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Abstract
The homeobox gene PROX1 is related to the Drosophila prospero gene, which is expressed in the developing central nervous system and lens‐secreting cone cells. We found that the PROX1 gene had missense and nonsense mutations in 4 of 29 hematologic cell lines analyzed. Decreased mRNA expression was also observed in half of these cell lines by RT‐PCR. The restoration of PROX1 gene expression after treatment with the demethylating agent 5‐aza‐2′‐deoxycytidine, as well as bisulfite sequencing analysis, indicated that gene silencing is caused by DNA hypermethylation at intron 1. Such hypermethylation was also seen in primary lymphomas (56.3%, 18/32) in a tumor‐specific manner. These findings indicate that the profile of the PROX1 gene corresponds to that of a candidate tumor‐suppressor gene.

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