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 language | English (US) |
|---|---|
| Article number | e38986 |
| Journal | eLife |
| Volume | 8 |
| DOIs | |
| State | Published - Mar 1 2019 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
Cite this
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 journal › Article
}
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 -