胸部肿瘤内科知识库

De novo promoter DNA methylation represses gene transcription and is a common mechanism to inactivate tumor suppressor genes in tumorigenesis. DNMT3B plays an important role in de novo DNA methylation. We report here the identification of a novel DNMT3B subfamily, termed Delta DNMT3B, whose expression is initiated through a promoter located at intron 4 and exon 5 of the DNMT3B gene. At least 7 transcriptional variants of Delta DNMT3B have been observed as the result of alternative pre-mRNA splicing. Predicted proteins derived from these variants suggest that 4 of the variants share a conservative enzymatic domain but contain a variable PWWP motif, a putative DNA binding structure, whereas 3 of the variants lack the enzymatic domain due to predicted premature translational termination. In non-small cell lung cancer (NSCLC) cell lines, Delta DNMT3B variants are frequently expressed and are the predominant forms of DNMT3B. Similarly, Delta DNMT3B variants are frequently expressed in primary NSCLC but are not detectable or are expressed at low levels in corresponding normal lung tissue. Our results indicate that Delta DNMT3B is the major expression form of DNMT3B in NSCLC and may play an important role in the development of aberrant promoter methylation during lung tumorigenesis.