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ResearchIn-Press PreviewCell biologyGeneticsOncology Open Access | 10.1172/JCI201343

ATRX loss predicts poor outcomes and sensitizes to TEAD inhibition in soft tissue sarcomas

Ryan A. Denu,1 Anand K. Singh,2 Yingda Jiang,2 Zhao Zheng,2 Davis R. Ingram,3 Khalida M. Wani,3 Rossana Lazcano,3 Madison P. Ginn,4 Kumaren Anand,5 Bishal K. Singh,2 Jackson C. Ballard,5 Veena Kochat,2 Biji Chatterjee,2 William Padron,2 Sharon M. Landers,6 Angela D. Bhalla,6 Asha S. Multani,7 Sharvari Dharmaiah,3 Prit Benny Malgulwar,3 Yiming Cai,8 Jun Yao,8 Heather Lin,9 Jason T. Huse,3 Haoqiang Ying,8 Emily Z. Keung,6 Wei-Lien Wang,3 Anthony P. Conley,1 Shreyaskumar Patel,1 Neeta Somaiah,1 Ahsan S. Farooqi,10 Alexander J. Lazar,2 Elise F. Nassif Haddad,1 Keila E. Torres,6 and Kunal Rai2

1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Torres, K. in: PubMed | Google Scholar

1Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

2Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, United States of America

3Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America

4University of Texas Health Sciences Center at Houston, Houston, United States of America

5Rice University, Houston, United States of America

6Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

7Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States of America

8Department of Molecular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, United States of America

10Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

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Published November 10, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI201343.
Copyright © 2026, Denu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 10, 2026 - Version history
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Abstract

ATRX is one of the most frequently altered genes in sarcoma and encodes an ATP-dependent chromatin remodeler implicated in maintaining heterochromatin. However, ATRX alterations have not been leveraged for sarcoma treatment. We observed loss of ATRX protein in 14% of soft tissue leiomyosarcoma (STLMS, n =127), 53% of uterine leiomyosarcoma (ULMS, n = 95), 37% of undifferentiated pleomorphic sarcoma (UPS, n = 82), and 8% of dedifferentiated liposarcoma (DDLPS, n = 84). ATRX loss was associated with significantly worse outcomes in ULMS, UPS, and DDLPS. ATRX knockout in sarcoma cells increased proliferation in cooperation with TP53 deletion, chromatin remodeling, and enrichment of PRDM4 and NFIX transcription factor motifs. PRDM4 and NFIX knockdown in ATRX-mutant sarcoma lines resulted in reduced proliferation and invasion, suggesting an epistatic relationship. Consistent with the known and re-demonstrated functional relationship between PRMD4 and YAP1, ATRX loss activated YAP1-TEAD signaling, and ATRX-deficient cells and sarcoma xenografts were more sensitive to the TEAD inhibitors VT103 and IAG933. Overall, our results identify ATRX loss as a prognostic factor of worse outcomes, implicate the ATRX-PRDM4-YAP1-TEAD axis as an underlying mechanism, and suggest use of TEAD inhibition as a potential therapeutic strategy for ATRX-deficient sarcomas.

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