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

Xiaodong Sun; Henry F. Frierson; Ceshi Chen; Changling Li; Qimei Ran; Kristen B. Otto; Brandi M. Cantarel; Robert L. Vessella; Allen C. Gao; John Petros; Yutaka Miura; Jonathan W. Simons; Jin Tang Dong

doi:10.1038/ng1528

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

Xiaodong Sun, Henry F. Frierson, Ceshi Chen, Changling Li, Qimei Ran, Kristen B. Otto, Brandi M. Cantarel, Robert L. Vessella, Allen C. Gao, John Petros, Yutaka Miura, Jonathan W. Simons, Jin Tang Dong

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146 Scopus citations

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^1-4. Here we report that ATBF1, which encodes a transcription factor that negatively regulates AFP and MYB ^5,6 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.

Original language	English (US)
Pages (from-to)	407-412
Number of pages	6
Journal	Nature genetics
Volume	37
Issue number	4
DOIs	https://doi.org/10.1038/ng1528
State	Published - Apr 2005

ASJC Scopus subject areas

Genetics

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@article{c4f7aa4921784843b7bb361c8b360a7e,

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 identified1-4. Here we report that ATBF1, which encodes a transcription factor that negatively regulates AFP and MYB 5,6 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.",

author = "Xiaodong Sun and Frierson, {Henry F.} and Ceshi Chen and Changling Li and Qimei Ran and Otto, {Kristen B.} and Cantarel, {Brandi M.} and Vessella, {Robert L.} and Gao, {Allen C.} and John Petros and Yutaka Miura and Simons, {Jonathan W.} and Dong, {Jin Tang}",

note = "Funding Information: 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.",

year = "2005",

month = apr,

doi = "10.1038/ng1528",

language = "English (US)",

volume = "37",

pages = "407--412",

journal = "Nature genetics",

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T1 - Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer

AU - Sun, Xiaodong

AU - Frierson, Henry F.

AU - Chen, Ceshi

AU - Li, Changling

AU - Ran, Qimei

AU - Otto, Kristen B.

AU - Cantarel, Brandi M.

AU - Vessella, Robert L.

AU - Gao, Allen C.

AU - Petros, John

AU - Miura, Yutaka

AU - Simons, Jonathan W.

AU - Dong, Jin Tang

N1 - Funding Information: 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.

PY - 2005/4

Y1 - 2005/4

N2 - 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 identified1-4. Here we report that ATBF1, which encodes a transcription factor that negatively regulates AFP and MYB 5,6 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.

AB - 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 identified1-4. Here we report that ATBF1, which encodes a transcription factor that negatively regulates AFP and MYB 5,6 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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Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer

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