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The genomic and epigenomic evolutionary history of papillary renal cell carcinomas.

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.

journal_name

Nat Commun

journal_title

Nature communications

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 DC,Chanoc

doi

10.1038/s41467-020-16546-5

subject

Has Abstract

pub_date

2020-06-18 00:00:00

pages

3096

issue

1

issn

2041-1723

pii

10.1038/s41467-020-16546-5

journal_volume

11

pub_type

杂志文章

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