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    The genomic and epigenomic evolutionary history of papillary renal cell carcinomas

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    Authors
    Zhu, B
    Poeta, ML
    Costantini, M
    Zhang, T
    Shi, J
    Sentinelli, S
    Zhao, W
    Pompeo, V
    Cardelli, M
    Alexandrov, BS
    Otlu, B
    Hua, X
    Jones, K
    Brodie, S
    Dabrowska, ME
    Toro, JR
    Yeager, M
    Wang, M
    Hicks, B
    Alexandrov, LB
    Brown, KM
    Wedge, David C
    Chanock, S
    Fazio, VM
    Gallucci, M
    Landi, MT
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    Affiliation
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, 20892, USA.
    Issue Date
    2020
    
    Metadata
    Show full item record
    Abstract
    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.
    Citation
    Zhu B, Poeta ML, Costantini M, Zhang T, Shi J, Sentinelli S, et al. The genomic and epigenomic evolutionary history of papillary renal cell carcinomas. Nat Commun. 2020;11(1):3096.
    Journal
    Nature Communications
    URI
    http://hdl.handle.net/10541/623146
    DOI
    10.1038/s41467-020-16546-5
    PubMed ID
    32555180
    Additional Links
    https://dx.doi.org/10.1038/s41467-020-16546-5
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-020-16546-5
    Scopus Count
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    All Paterson Institute for Cancer Research

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