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Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer

Nature Genetics volume 37, pages 407–412 (2005)Cite this article

A Corrigendum to this article was published on 01 June 2005

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 identified1,2,3,4. Here we report that ATBF1, which encodes a transcription factor that negatively regulates AFP and MYB5,6 but transactivates CDKN1A7, 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.

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Figure 1: Deletion mapping of the 16q22 locus in prostate cancer.
Figure 2: Reduced expression of ATBF1 in prostatic cancer cells.
Figure 3: Detection of ATBF1 mutations in prostate cancer samples by PCR-SSCP analysis.
Figure 4: Aberrant splicing of ATBF1 in cell lines with deletions in the polypyrimidine tract in intron 8.
Figure 5: Suppression of cell proliferation by ATBF1.

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Acknowledgements

We thank L.W.K. Chung for his encouragement. This work was supported by grants from the National Cancer Institute, Department of Defense Prostate Cancer Research Program, and the Georgia Cancer Coalition.

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Author notes

  1. Henry F Frierson and Ceshi Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, 30322, Georgia, USA

    Xiaodong Sun, Ceshi Chen, Qimei Ran, Kristen B Otto, Jonathan W Simons & Jin-Tang Dong

  2. Department of Pathology, University of Virginia Health System, Charlottesville, 22901, Virginia, USA

    Henry F Frierson

  3. Department of Urological Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, 100021, China

    Changling Li

  4. Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, 22901, Virginia, USA

    Brandi M Cantarel

  5. Department of Urology, University of Washington Medical Center, Seattle, 98195, Washington, USA

    Robert L Vessella

  6. Departments of Medicine and Pharmacology, Roswell Park Cancer Institute, Buffalo, 14263, New York, USA

    Allen C Gao

  7. Departments of Urology and Pathology, Emory University School of Medicine, Atlanta, 30322, Georgia, USA

    John Petros

  8. Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan

    Yutaka Miura

  9. Department of Urology and Program in Genetics and Molecular Biology, Emory University School of Medicine, Atlanta, 30322, Georgia, USA

    Jin-Tang Dong

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Correspondence to Jin-Tang Dong.

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Supplementary information

Supplementary Fig. 1

Examples of sequencing results showing the affected nucleotide in a case. (PDF 188 kb)

Supplementary Table 1

Short mononucleotide tracts and their alterations in tumor and normal samples. (PDF 18 kb)

Supplementary Table 2

Summary of nucleotide alterations considered as polymorphisms. (PDF 22 kb)

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Sun, X., Frierson, H., Chen, C. et al. Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer. Nat Genet 37, 407–412 (2005). https://doi.org/10.1038/ng1528

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