Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma

Author:

Xu Jianing1,Reznik Ed23ORCID,Lee Ho-Joon45,Gundem Gunes23,Jonsson Philip13,Sarungbam Judy6,Bialik Anna6,Sanchez-Vega Francisco13,Creighton Chad J78,Hoekstra Jake9,Zhang Li4,Sajjakulnukit Peter4,Kremer Daniel410,Tolstyka Zachary4,Casuscelli Jozefina11,Stirdivant Steve12,Tang Jie13,Schultz Nikolaus123,Jeng Paul1,Dong Yiyu1,Su Wenjing14,Cheng Emily H16,Russo Paul15,Coleman Jonathan A15,Papaemmanuil Elli23,Chen Ying-Bei6ORCID,Reuter Victor E6,Sander Chris1617,Kennedy Scott R9,Hsieh James J18,Lyssiotis Costas A419,Tickoo Satish K6,Hakimi A Ari1ORCID

Affiliation:

1. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, United States

2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States

3. Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, United States

4. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, United States

5. Rogel Cancer Center, University of Michigan, Ann Arbor, United States

6. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States

7. Human Genome Sequencing Center, Baylor College of Medicine, Houston, United States

8. Department of Medicine, Baylor College of Medicine, Houston, United States

9. Department of Pathology, University of Washington, Seattle, United States

10. Graduate Program in Chemical Biology, University of Michigan, Ann Arbor, United States

11. Department of Urology, Ludwig-Maximilians University, Munich, Germany

12. Metabolon Inc, Durham, United States

13. Genomics Core, Cedars-Sinai Medical Center, Los Angeles, United States

14. Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, United States

15. Department of Urology, Memorial Sloan Kettering Cancer Center, New York, United States

16. cBio Center, Dana-Farber Cancer Institute, Boston, United States

17. Department of Cell Biology, Harvard Medical School, Boston, United States

18. Department of Medicine, Molecular Oncology, Siteman Cancer Center, Washington University, St. Louis, United States

19. Department of Internal Medicine, Division of Gastroenterology, Rogel Cancer Center, University of Michigan, Ann Arbor, United States

Abstract

While genomic sequencing routinely identifies oncogenic alterations for the majority of cancers, many tumors harbor no discernable driver lesion. Here, we describe the exceptional molecular phenotype of a genomically quiet kidney tumor, clear cell papillary renal cell carcinoma (CCPAP). In spite of a largely wild-type nuclear genome, CCPAP tumors exhibit severe depletion of mitochondrial DNA (mtDNA) and RNA and high levels of oxidative stress, reflecting a shift away from respiratory metabolism. Moreover, CCPAP tumors exhibit a distinct metabolic phenotype uniquely characterized by accumulation of the sugar alcohol sorbitol. Immunohistochemical staining of primary CCPAP tumor specimens recapitulates both the depletion of mtDNA-encoded proteins and a lipid-depleted metabolic phenotype, suggesting that the cytoplasmic clarity in CCPAP is primarily related to the presence of glycogen. These results argue for non-genetic profiling as a tool for the study of cancers of unknown driver.

Funder

Damon Runyon Cancer Research Foundation

V Foundation for Cancer Research

Sidney Kimmel Foundation for Cancer Research

National Institutes of Health

Charles Woodson Research Fund

The UM Pediatric Brain Tumor Initiative

University of Michigan

National Cancer Institute

American Urological Association

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Cited by 31 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3