title: Mutational analysis of  DNMT3A  gene in acute leukemias and common solid cancers.
abstract: DNMT3A, a DNA methyltransferase that functions for de novo methylation, is important in development and many cellular processes related to tumorigenesis. Somatic mutations of DNMT3A gene, including recurrent mutations in its Arg-882, were recently reported in acute myelogenous leukemia (AML), strongly suggesting its role in development of AML. To see whether DNMT3A mutation occurs in other malignancies as well, we analyzed DNMT3A in 916 cancer tissues from 401 hematologic malignancies (AML, acute lymphoblastic leukemias (ALL), multiple myelomas and lymphomas) and 515 carcinomas (lung, breast, prostate, colorectal and gastric carcinomas) using a single-strand conformation polymorphism (SSCP) assay. We identified DNMT3A mutations, especially the Arg-882 mutations, in adulthood AML (9.4%). In addition, we found DNMT3A mutations in pre-B-ALL and three lung cancers at lower frequencies. Allelic loss of DNMT3A was frequently observed in most cancer types analyzed, including lymphomas (48.1%), gastric cancers (23.5%) and lung cancers (18.3%) irrespective of DNMT3A mutation. Also, loss of DNMT3A expression was common in lung cancers (46.4%), and was associated with the allelic loss. Our data indicate that DNMT3A gene is mutated mainly in AML, but it occurs in other cancers, such as ALL and lung cancer, despite the lower incidences. Also, the data suggest that DNMT3A is altered in many cancer types by various ways, including somatic mutations, allelic loss and loss of expression that might play roles in tumorigenesis.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Min S
authors.initials: MS
authors.lastname: Kim
authors.forename: Yoo R
authors.initials: YR
authors.lastname: Kim
authors.forename: Nam J
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Sug H
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000208:Acute Disease; D000328:Adult; D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D002648:Child; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics; D056910:Republic of Korea; D013274:Stomach Neoplasms / Q000235:genetics; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human