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Research Article

DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer

  • Steven T. Lott,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Nanyue Chen,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Dawn S. Chandler,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Qifeng Yang,

    Affiliation: Department of Radiation Oncology, University of Medicine & Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America

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  • Luo Wang,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Marivonne Rodriguez,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Hongyan Xie,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Seetharaman Balasenthil,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Thomas A. Buchholz,

    Affiliation: Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Aysegul A. Sahin,

    Affiliation: Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Katrina Chaung,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Baili Zhang,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Shodimu-Emmanu Olufemi,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Jinyun Chen,

    Affiliation: Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Henry Adams,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Vimla Band,

    Affiliation: Department of Genetics, Cell Biology and Anatomy, The University of Nebraska Medical Center, Eppley Cancer Center, Omaha, Nebraska, United States of America

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  • Adel K. El-Naggar,

    Affiliation: Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Marsha L. Frazier,

    Affiliation: Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Khandan Keyomarsi,

    Affiliation: Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Kelly K. Hunt,

    Affiliation: Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Subrata Sen,

    Affiliation: Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Bruce Haffty,

    Affiliation: Department of Radiation Oncology, University of Medicine & Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America

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  • Stephen M. Hewitt,

    Affiliation: Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Ralf Krahe,

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Ann McNeill Killary mail

    akillary@mdanderson.org

    Affiliation: Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America

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  • Published: May 05, 2009
  • DOI: 10.1371/journal.pmed.1000068

About the Authors

Steven T. Lott, Nanyue Chen, Dawn S. Chandler, Luo Wang, Marivonne Rodriguez, Hongyan Xie, Seetharaman Balasenthil, Katrina Chaung, Baili Zhang, Shodimu-Emmanu Olufemi, Henry Adams, Ralf Krahe, Ann McNeill Killary
Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America
Qifeng Yang, Bruce Haffty
Department of Radiation Oncology, University of Medicine & Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
Thomas A. Buchholz
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America
Aysegul A. Sahin, Adel K. El-Naggar, Subrata Sen
Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America
Jinyun Chen, Marsha L. Frazier
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America
Vimla Band
Department of Genetics, Cell Biology and Anatomy, The University of Nebraska Medical Center, Eppley Cancer Center, Omaha, Nebraska, United States of America
Khandan Keyomarsi
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America
Kelly K. Hunt
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America
Stephen M. Hewitt
Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America

Corresponding Author

Email: akillary@mdanderson.org

Competing Interests

STL, DSC, and AMK are co-inventors named in the US Patent #6,943,245 granted 9/13/2005 and US Patent #7,169,384 granted 1/30/2007 to the University of Texas M. D. Anderson Cancer Center regarding the novel gene DEAR1 described herein.

Author Contributions

ICMJE criteria for authorship read and met: STL NC DSC QY LW MR HX SB TB AS KC BZ SEO JC HA VB AKEN MLF KK KKH SS BH SMH RK AK. Agree with the manuscript's results and conclusions: STL NC DSC QY LW MR HX SB TB AS KC BZ SEO JC HA VB AKEN MLF KK KKH SS BH SMH RK AK. Designed the experiments/the study: STL NC DSC BZ RK AK. Analyzed the data: STL NC DSC LW MR HX SB TB AS KC BZ HA MLF KKH SS BH SMH RK AK. Collected data/did experiments for the study: STL NC DSC QY LW BZ SEO JC KKH SMH RK. Enrolled patients: KKH. Wrote the first draft of the paper: DSC AK. Contributed to the writing of the paper: STL NC DSC QY LW VB MLF KK SS BH SMH RK. Conceived of and/or performed many of the experiments in the paper: STL. Designed some experiments, DEAR1 knock-down assay and DEAR1 antibody confirmation by Western: NC. Performed experiments, collected data, and analyzed experiments as well as made the revised figures: NC. Contributed to the identification of the homozygous deletion: LW. Collected sequencing, gene expression, and acinar morphogenesis data: MR. Helped in the identification of a missense mutation in DEAR1 by direct sequencing: KC. Designed and analyzed results from methylation assays: BZ. Analyzed and interpreted data: JC. Performed imaging of 3D cultures and helped with interpretation of the imaging data: HA. Provided 21T series cells and protocols and consultation in culture and 3D acinar structure of these cells: VB. Provided materials: AKEN. Assisted in the evaluation of results: AKEN. Helped design some of the experiments: MLF. Provided some of the sequencing data: MLF. Helped in experiments analyzing expression of DEAR1 gene in breast cancer cells: SS. Gave comments and suggestions on the draft manuscript: SS. Interpreted and photographed immunohistochemistry in some figures: SMH. Collected pyrosequencing data and supervised BZ and SEO in experimentation, data generation, and analysis: RK. Conceived of most of the experiments in the paper, including the experiments that led to the cloning, identification, and characterization of DEAR1 and its role as a regulator of acinar morphogenesis and independent predictor of recurrence-free survival in early onset breast cancer: AK. Supervised or initiated the collaboration for most of the experiments in the manuscript: AK.