Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer.
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.
Sun
Xiaodong
X
Winship Cancer Institute, Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Frierson
Henry F
HF
Chen
Ceshi
C
Li
Changling
C
Ran
Qimei
Q
Otto
Kristen B
KB
Cantarel
Brandi L
BL
Cantarel
Brandi M
BM
Vessella
Robert L
RL
Gao
Allen C
AC
Petros
John
J
Miura
Yutaka
Y
Simons
Jonathan W
JW
Dong
Jin-Tang
JT
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
D018398:Homeodomain Proteins; D012333:RNA, Messenger; C071660:ZFHX3 protein, human