title: Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer.
abstract: Cancer often results from the accumulation of multiple genetic alterations. Although most malignancies are sporadic, only a small number of genes have been shown to undergo frequent mutations in sporadic cancers. The long arm of chromosome 16 is frequently deleted in human cancers, but the target gene for this deletion has not been identified. Here we report that ATBF1, which encodes a transcription factor that negatively regulates AFP and MYB but transactivates CDKN1A, is a good candidate for the 16q22 tumor-suppressor gene. We narrowed the region of deletion at 16q22 to 861 kb containing ATBF1. ATBF1 mRNA was abundant in normal prostates but more scarce in approximately half of prostate cancers tested. In 24 of 66 (36%) cancers examined, we identified 22 unique somatic mutations, many of which impair ATBF1 function. Furthermore, ATBF1 inhibited cell proliferation. Hence, loss of ATBF1 is one mechanism that defines the absence of growth control in prostate cancer.
authors.affiliation: Winship Cancer Institute, Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.forename: Henry F
authors.initials: HF
authors.lastname: Frierson
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
authors.forename: Changling
authors.initials: C
authors.lastname: Li
authors.forename: Qimei
authors.initials: Q
authors.lastname: Ran
authors.forename: Kristen B
authors.initials: KB
authors.lastname: Otto
authors.forename: Brandi L
authors.initials: BL
authors.lastname: Cantarel
authors.forename: Brandi M
authors.initials: BM
authors.lastname: Cantarel
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.forename: Allen C
authors.initials: AC
authors.lastname: Gao
authors.forename: John
authors.initials: J
authors.lastname: Petros
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miura
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Simons
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
mesh_terms: D049109:Cell Proliferation; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; C071660:ZFHX3 protein, human