title: Characterization of the imprinted polycomb gene L3MBTL, a candidate 20q tumour suppressor gene, in patients with myeloid malignancies.
abstract: Chromosome 20q deletion is a recurrent chromosomal abnormality associated with myeloid malignancies. L3MBTL represents a strong candidate tumour suppressor gene since it lies within the common deleted region, is a member of the Polycomb-like family, encodes the human homologue of a Drosophila tumour suppressor and is expressed within haematopoietic progenitor cells. We describe the structure of L3MBTL, identify two putative promoters each associated with two CpG islands and characterize a complex pattern of alternative splicing events. Mutation analysis of the gene in patients with and without a 20q deletion identified several polymorphisms but no acquired mutations. The two CpG islands spanning promoter 2 undergo monoallelic methylation in normal haematopoietic cells consistent with imprinting of L3MBTL. Samples from patients with a 20q deletion retained either the methylated or unmethylated allele but retention of the methylated allele did not correlate with reduction in L3MBTL mRNA levels. The absence of a correlation between L3MBTL methylation and transcription could be shown to reflect loss of imprinting in one patient. In addition, our results demonstrate that inactivation of L3MBTL is not a common occurrence in patients with a 20q deletion or in cytogenetically normal patients with polycythaemia vera.
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bench
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Brian J P
authors.initials: BJ
authors.lastname: Huntly
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Nasios
authors.initials: N
authors.lastname: Fourouclas
authors.forename: Adrienne R
authors.initials: AR
authors.lastname: Hunt
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Green
mesh_terms: D017398:Alternative Splicing; D001855:Bone Marrow Diseases / Q000235:genetics*; D016022:Case-Control Studies; D002868:Chromosomal Proteins, Non-Histone; D002872:Chromosome Deletion; D018899:CpG Islands; D004252:DNA Mutational Analysis; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D008745:Methylation; D009190:Myelodysplastic Syndromes / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C120887:L3MBTL1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins