The genomic and epigenomic evolutionary history of papillary renal cell carcinomas

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2020-06-01
Zhu, Bin
Poeta, Maria Luana
Costantini, Manuela
Zhang, Tongwu
Shi, Jianxin
Sentinelli, Steno
Zhao, Wei
Pompeo, Vincenzo
Cardelli, Maurizio
Alexandrov, Boian S.
Otlu Sarıtaş, Burçak
Hua, Xing
Jones, Kristine
Brodie, Seth
Dabrowska, Malgorzata Ewa
Toro, Jorge R.
Yeager, Meredith
Wang, Mingyi
Hicks, Belynda
Alexandrov, Ludmil B.
Brown, Kevin M.
Wedge, David C.
Chanock, Stephen
Fazio, Vito Michele
Gallucci, Michele
Landi, Maria Teresa
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, in pRCC, driver gene mutations and most arm-level somatic copy number alterations (SCNAs) are clonal. These findings suggest that a single biopsy would be sufficient to identify the important genetic drivers and that targeting large-scale SCNAs may improve pRCC treatment, which is currently poor. While type 1 pRCC displays near absence of structural variants (SVs), the more aggressive type 2 pRCC and the rarer subtypes have numerous SVs, which should be pursued for prognostic significance. Many tumours are heterogenous, which calls into question whether multiple biopsies are required to accurately assess the cancer. Here, the authors show that papillary renal cell carcinoma is clonal in nature, suggesting that in this cancer one biopsy is sufficient for diagnosis and molecular analyses.
https://hdl.handle.net/11511/97293
NATURE COMMUNICATIONS
Graduate School of Informatics, Article

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Citation Formats
B. Zhu et al., “The genomic and epigenomic evolutionary history of papillary renal cell carcinomas,” NATURE COMMUNICATIONS, vol. 11, no. 1, pp. 0–0, 2020, Accessed: 00, 2022. [Online]. Available: https://hdl.handle.net/11511/97293.
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