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Comprehensive Molecular Characterization Identifies Distinct Genomic and Immune Hallmarks of Renal Medullary Carcinoma

86 Pages Posted: 19 Sep 2019 Publication Status: Published

See all articles by Pavlos Msaouel

Pavlos Msaouel

University of Texas at Houston - Department of Genitourinary Medical Oncology

Gabriel G. Malouf

University of Strasbourg - Department of Hematology and Oncology

Xiaoping Su

University of Texas at Houston - Department of Bioinformatics and Computational Biology

Hui Yao

University of Texas at Houston - Department of Bioinformatics and Computational Biology

Durga N. Tripathi

Baylor University - Center for Precision Environmental Health

Jianjun Gao

University of Texas at Houston - Department of Genitourinary Medical Oncology

Priya Rao

University of Texas at Houston - Department of Pathology

Cristian Coarfa

Baylor University - Department of Molecular and Cellular Biology; Baylor University - Advanced Technology Core Labs

Chad J. Creighton

University of Texas at Houston - Department of Bioinformatics and Computational Biology

Asha S. Multani

University of Texas at Houston - Department of Genetics

Jorge Blando

University of Texas at Houston - Department of Immunology

Rong He

University of Texas at Houston - Department of Genitourinary Medical Oncology

Melinda Soeung

University of Texas at Houston - Department of Genomic Medicine

Luigi Perelli

University of Texas at Houston - Department of Genitourinary Medical Oncology

Sanjana Srinivasan

University of Texas at Houston - Department of Genomic Medicine

Jean-Philippe Bertocchio

University of Texas at Houston - Department of Genitourinary Medical Oncology

Patrick G. Pilié

University of Texas at Houston - Department of Genitourinary Medical Oncology

Menuka Karki

Baylor college of Medicine - Center for Precision Environmental Health

Riyad N.H. Seervai

Baylor college of Medicine - Center for Precision Environmental Health

Dolores Lopez-Terrada

Baylor University - Department of Pathology

Ximing Tang

University of Texas at Houston - Department of Translational Molecular Pathology

Wei Lu

University of Texas at Houston - Department of Translational Molecular Pathology

Ignacio I. Wistuba

University of Texas at Houston - Department of Translational Molecular Pathology

Virginia Giuliani

University of Texas at Houston - Institute for Applied Cancer Science

Alessandro Carugo

University of Texas at Houston - Institute for Applied Cancer Science

Timothy P. Heffernan

University of Texas at Houston - Institute for Applied Cancer Science

Padmanee Sharma

University of Texas at Houston - Department of Immunology

Jose A. Karam

University of Texas at Houston - Department of Urology

Christopher G. Wood

University of Texas at Houston - Department of Urology

Cheryl L. Walker

Baylor college of Medicine - Center for Precision Environmental Health

Giannicola Genovese

University of Texas at Houston - Department of Genitourinary Medical Oncology

Nizar M. Tannir

University of Texas at Houston - Department of Genitourinary Medical Oncology

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Abstract

Renal medullary carcinoma (RMC) is a highly lethal malignancy that mainly afflicts young individuals of African descent and is resistant to all targeted agents used to treat other renal cell carcinomas. Comprehensive genomic and transcriptomic profiling of untreated primary RMC tissues was performed to elucidate the molecular landscape of these tumors. We found that RMC was characterized by high replication stress and an abundance of focal copy number alterations associated with activation of the stimulator of the cyclic GMP-AMP synthase interferon genes (cGAS-STING) innate immune pathway. Replication stress conferred a therapeutic vulnerability to drugs targeting DNA damage repair pathways. Elucidation of these previously unknown RMC hallmarks paves the way to new clinical trials for this rare but highly lethal malignancy.

Keywords: Molecular profiling, renal medullary carcinoma, replication stress, SMARCB1, cGAS-STING pathway

Suggested Citation

Msaouel, Pavlos and Malouf, Gabriel G. and Su, Xiaoping and Yao, Hui and Tripathi, Durga N. and Gao, Jianjun and Rao, Priya and Coarfa, Cristian and Creighton, Chad J. and Multani, Asha S. and Blando, Jorge and He, Rong and Soeung, Melinda and Perelli, Luigi and Srinivasan, Sanjana and Bertocchio, Jean-Philippe and Pilié, Patrick G. and Karki, Menuka and Seervai, Riyad N.H. and Lopez-Terrada, Dolores and Tang, Ximing and Lu, Wei and Wistuba, Ignacio I. and Giuliani, Virginia and Carugo, Alessandro and Heffernan, Timothy P. and Sharma, Padmanee and Karam, Jose A. and Wood, Christopher G. and Walker, Cheryl L. and Genovese, Giannicola and Tannir, Nizar M., Comprehensive Molecular Characterization Identifies Distinct Genomic and Immune Hallmarks of Renal Medullary Carcinoma (September 16, 2019). Available at SSRN: https://ssrn.com/abstract=3454866 or http://dx.doi.org/10.2139/ssrn.3454866
This version of the paper has not been formally peer reviewed.

Pavlos Msaouel (Contact Author)

University of Texas at Houston - Department of Genitourinary Medical Oncology ( email )

1901 East Road, Unit 1950
Houston, TX 77030
United States

Gabriel G. Malouf

University of Strasbourg - Department of Hematology and Oncology

Strasbourg
France

Xiaoping Su

University of Texas at Houston - Department of Bioinformatics and Computational Biology

1515 Holocombe Blvd
1400 Pressler St., Floor 4, FCT4.6000
Houston, TX 77030
United States

Hui Yao

University of Texas at Houston - Department of Bioinformatics and Computational Biology

Pickens Academic Tower
1400 Pressler St., Floor 4, FCT4.6000
Houston, TX 77230-1402
United States

Durga N. Tripathi

Baylor University - Center for Precision Environmental Health

Alkek Building, Suite N1317.00
One Baylor Plaza, BCM229
Houston, TX 77030-3411
United States

Jianjun Gao

University of Texas at Houston - Department of Genitourinary Medical Oncology

1901 East Road, Unit 1950
Houston, TX 77030
United States

Priya Rao

University of Texas at Houston - Department of Pathology

1515 Holcombe Boulevard
Houston, TX 77030
United States

Cristian Coarfa

Baylor University - Department of Molecular and Cellular Biology ( email )

Houston, TX
United States

Baylor University - Advanced Technology Core Labs ( email )

Houston, TX
United States

Chad J. Creighton

University of Texas at Houston - Department of Bioinformatics and Computational Biology

1515 Holocombe Blvd
1400 Pressler St., Floor 4, FCT4.6000
Houston, TX 77030
United States

Asha S. Multani

University of Texas at Houston - Department of Genetics

Houston, TX
United States

Jorge Blando

University of Texas at Houston - Department of Immunology

1515 Holocombe Blvd
Houston, TX 77030
United States

Rong He

University of Texas at Houston - Department of Genitourinary Medical Oncology

1901 East Road, Unit 1950
Houston, TX 77030
United States

Melinda Soeung

University of Texas at Houston - Department of Genomic Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Luigi Perelli

University of Texas at Houston - Department of Genitourinary Medical Oncology

1901 East Road, Unit 1950
Houston, TX 77030
United States

Sanjana Srinivasan

University of Texas at Houston - Department of Genomic Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Jean-Philippe Bertocchio

University of Texas at Houston - Department of Genitourinary Medical Oncology

1901 East Road, Unit 1950
Houston, TX 77030
United States

Patrick G. Pilié

University of Texas at Houston - Department of Genitourinary Medical Oncology

1901 East Road, Unit 1950
Houston, TX 77030
United States

Menuka Karki

Baylor college of Medicine - Center for Precision Environmental Health

Alkek Building, Suite N1317.00
One Baylor Plaza, BCM229
Houston, TX 77030-3411
United States

Riyad N.H. Seervai

Baylor college of Medicine - Center for Precision Environmental Health

Alkek Building, Suite N1317.00
One Baylor Plaza, BCM229
Houston, TX 77030-3411
United States

Dolores Lopez-Terrada

Baylor University - Department of Pathology

United States

Ximing Tang

University of Texas at Houston - Department of Translational Molecular Pathology

2130 West Holcombe Boulevard, Suite 910
Houston, TX 77030
United States

Wei Lu

University of Texas at Houston - Department of Translational Molecular Pathology

2130 West Holcombe Boulevard, Suite 910
Houston, TX 77030
United States

Ignacio I. Wistuba

University of Texas at Houston - Department of Translational Molecular Pathology

2130 West Holcombe Boulevard, Suite 910
Houston, TX 77030
United States

Virginia Giuliani

University of Texas at Houston - Institute for Applied Cancer Science

Houston, TX
United States

Alessandro Carugo

University of Texas at Houston - Institute for Applied Cancer Science

Houston, TX
United States

Timothy P. Heffernan

University of Texas at Houston - Institute for Applied Cancer Science

Houston, TX
United States

Padmanee Sharma

University of Texas at Houston - Department of Immunology

1515 Holocombe Blvd
Houston, TX 77030
United States

Jose A. Karam

University of Texas at Houston - Department of Urology

1515 Holcombe Blvd
Houston, TX 77230-1402
United States

Christopher G. Wood

University of Texas at Houston - Department of Urology

1515 Holcombe Blvd
Houston, TX 77230-1402
United States

Cheryl L. Walker

Baylor college of Medicine - Center for Precision Environmental Health ( email )

Alkek Building, Suite N1317.00
One Baylor Plaza, BCM229
Houston, TX 77030-3411
United States

Giannicola Genovese

University of Texas at Houston - Department of Genitourinary Medical Oncology ( email )

1901 East Road, Unit 1950
Houston, TX 77030
United States

Nizar M. Tannir

University of Texas at Houston - Department of Genitourinary Medical Oncology ( email )

1901 East Road, Unit 1950
Houston, TX 77030
United States

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