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

✍ Scribed by Hirokazu Nagai; Yinghua Li; Sonoko Hatano; Ohno Toshihito; Masayuki Yuge; Etsuro Ito; Makoto Utsumi; Hidehiko Saito; Tomohiro Kinoshita

Publisher
John Wiley and Sons
Year
2003
Tongue
English
Weight
324 KB
Volume
38
Category
Article
ISSN
1045-2257

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✦ Synopsis

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. © 2003 Wiley‐Liss, Inc.

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