title: Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies.
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.
authors.affiliation: 1st Department of Internal Medicine, Nagoya University School of Medicine, Showa-ku, Nagoya, Japan. nagaih@nnh.hosp.go.jp
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagai
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Li
authors.forename: Sonoko
authors.initials: S
authors.lastname: Hatano
authors.forename: Ohno
authors.initials: O
authors.lastname: Toshihito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yuge
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.forename: Makoto
authors.initials: M
authors.lastname: Utsumi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Saito
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D018922:HL-60 Cells; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007438:Introns / Q000235:genetics; D019169:Jurkat Cells; D020014:K562 Cells; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D013447:Sulfites / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D020298:U937 Cells; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D013447:Sulfites; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D001374:Azacitidine; C042345:hydrogen sulfite