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

Jianing Xu, Ed Reznik, Ho Joon Lee, Gunes Gundem, Philip Jonsson, Judy Sarungbam, Anna Bialik, Francisco Sanchez-Vega, Chad J. Creighton, Jake Hoekstra, Li Zhang, Peter Sajjakulnukit, Daniel Kremer, Zachary Tolstyka, Jozefina Casuscelli, Steve Stirdivant, Jie Tang, Nikolaus Schultz, Paul Jeng, Yiyu DongWenjing Su, Emily H. Cheng, Paul Russo, Jonathan A. Coleman, Elli Papaemmanui, Ying Bei Chen, Victor E. Reuter, Chris Sander, Scott R. Kennedy, James J. Hsieh, Costas A. Lyssiotis, Satish K. Tickoo, A. Ari Hakimi

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere38986
JournaleLife
Volume8
DOIs
StatePublished - Mar 1 2019
Externally publishedYes

Fingerprint

Renal Cell Carcinoma
Metabolism
Tumors
Cells
Neoplasms
Mitochondrial DNA
Phenotype
Sugar Alcohols
Oxidative stress
Sorbitol
Ports and harbors
Glycogen
Genes
Lipids
Oxidative Stress
Genome
Staining and Labeling
Kidney
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Xu, J., Reznik, E., Lee, H. J., Gundem, G., Jonsson, P., Sarungbam, J., ... Ari Hakimi, A. (2019). Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma. eLife, 8, [e38986]. https://doi.org/10.7554/eLife.38986

Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma. / Xu, Jianing; Reznik, Ed; Lee, Ho Joon; Gundem, Gunes; Jonsson, Philip; Sarungbam, Judy; Bialik, Anna; Sanchez-Vega, Francisco; Creighton, Chad J.; Hoekstra, Jake; Zhang, Li; Sajjakulnukit, Peter; Kremer, Daniel; Tolstyka, Zachary; Casuscelli, Jozefina; Stirdivant, Steve; Tang, Jie; Schultz, Nikolaus; Jeng, Paul; Dong, Yiyu; Su, Wenjing; Cheng, Emily H.; Russo, Paul; Coleman, Jonathan A.; Papaemmanui, Elli; Chen, Ying Bei; Reuter, Victor E.; Sander, Chris; Kennedy, Scott R.; Hsieh, James J.; Lyssiotis, Costas A.; Tickoo, Satish K.; Ari Hakimi, A.

In: eLife, Vol. 8, e38986, 01.03.2019.

Research output: Contribution to journalArticle

Xu, J, Reznik, E, Lee, HJ, Gundem, G, Jonsson, P, Sarungbam, J, Bialik, A, Sanchez-Vega, F, Creighton, CJ, Hoekstra, J, Zhang, L, Sajjakulnukit, P, Kremer, D, Tolstyka, Z, Casuscelli, J, Stirdivant, S, Tang, J, Schultz, N, Jeng, P, Dong, Y, Su, W, Cheng, EH, Russo, P, Coleman, JA, Papaemmanui, E, Chen, YB, Reuter, VE, Sander, C, Kennedy, SR, Hsieh, JJ, Lyssiotis, CA, Tickoo, SK & Ari Hakimi, A 2019, 'Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma', eLife, vol. 8, e38986. https://doi.org/10.7554/eLife.38986
Xu, Jianing ; Reznik, Ed ; Lee, Ho Joon ; Gundem, Gunes ; Jonsson, Philip ; Sarungbam, Judy ; Bialik, Anna ; Sanchez-Vega, Francisco ; Creighton, Chad J. ; Hoekstra, Jake ; Zhang, Li ; Sajjakulnukit, Peter ; Kremer, Daniel ; Tolstyka, Zachary ; Casuscelli, Jozefina ; Stirdivant, Steve ; Tang, Jie ; Schultz, Nikolaus ; Jeng, Paul ; Dong, Yiyu ; Su, Wenjing ; Cheng, Emily H. ; Russo, Paul ; Coleman, Jonathan A. ; Papaemmanui, Elli ; Chen, Ying Bei ; Reuter, Victor E. ; Sander, Chris ; Kennedy, Scott R. ; Hsieh, James J. ; Lyssiotis, Costas A. ; Tickoo, Satish K. ; Ari Hakimi, A. / Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma. In: eLife. 2019 ; Vol. 8.
@article{22c44d74f91247a99441cbe2703948b5,
title = "Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma",
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.",
author = "Jianing Xu and Ed Reznik and Lee, {Ho Joon} and Gunes Gundem and Philip Jonsson and Judy Sarungbam and Anna Bialik and Francisco Sanchez-Vega and Creighton, {Chad J.} and Jake Hoekstra and Li Zhang and Peter Sajjakulnukit and Daniel Kremer and Zachary Tolstyka and Jozefina Casuscelli and Steve Stirdivant and Jie Tang and Nikolaus Schultz and Paul Jeng and Yiyu Dong and Wenjing Su and Cheng, {Emily H.} and Paul Russo and Coleman, {Jonathan A.} and Elli Papaemmanui and Chen, {Ying Bei} and Reuter, {Victor E.} and Chris Sander and Kennedy, {Scott R.} and Hsieh, {James J.} and Lyssiotis, {Costas A.} and Tickoo, {Satish K.} and {Ari Hakimi}, A.",
year = "2019",
month = "3",
day = "1",
doi = "10.7554/eLife.38986",
language = "English (US)",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma

AU - Xu, Jianing

AU - Reznik, Ed

AU - Lee, Ho Joon

AU - Gundem, Gunes

AU - Jonsson, Philip

AU - Sarungbam, Judy

AU - Bialik, Anna

AU - Sanchez-Vega, Francisco

AU - Creighton, Chad J.

AU - Hoekstra, Jake

AU - Zhang, Li

AU - Sajjakulnukit, Peter

AU - Kremer, Daniel

AU - Tolstyka, Zachary

AU - Casuscelli, Jozefina

AU - Stirdivant, Steve

AU - Tang, Jie

AU - Schultz, Nikolaus

AU - Jeng, Paul

AU - Dong, Yiyu

AU - Su, Wenjing

AU - Cheng, Emily H.

AU - Russo, Paul

AU - Coleman, Jonathan A.

AU - Papaemmanui, Elli

AU - Chen, Ying Bei

AU - Reuter, Victor E.

AU - Sander, Chris

AU - Kennedy, Scott R.

AU - Hsieh, James J.

AU - Lyssiotis, Costas A.

AU - Tickoo, Satish K.

AU - Ari Hakimi, A.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85064573309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064573309&partnerID=8YFLogxK

U2 - 10.7554/eLife.38986

DO - 10.7554/eLife.38986

M3 - Article

C2 - 30924768

AN - SCOPUS:85064573309

VL - 8

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e38986

ER -