Timing the landmark events in the evolution of clear cell renal cell cancer: TRACERx renal
Author(s)
Type
Journal Article
Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the 5′ UTR of TERT, targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening. The most common structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. This event occurs in childhood or adolescence, generally as the initiating event that precedes emergence of the tumor’s most recent common ancestor by years to decades. Similar genomic changes drive inherited ccRCC. Modeling differences in age incidence between inherited and sporadic cancers suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred. Early development of ccRCC follows well-defined evolutionary trajectories, offering opportunity for early intervention.
Date Issued
2018-04-19
Date Acceptance
2018-02-07
Citation
Cell, 2018, 173 (3), pp.611-623.e1-e8
ISSN
0092-8674
Publisher
Elsevier (Cell Press)
Start Page
611
End Page
623.e1-e8
Journal / Book Title
Cell
Volume
173
Issue
3
Copyright Statement
© 2018 Crown Copyright. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 InterNational licence (CC-BY 4.0 - https://creativecommons.org/licenses/by/4.0/)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000430677400012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
TERT PROMOTER MUTATIONS
COPY-NUMBER
SOMATIC MUTATIONS
KIDNEY CANCER
HTERT GENE
C-MYC
CARCINOMA
CHROMOTHRIPSIS
TRANSCRIPTION
PATTERNS
Publication Status
Published
Date Publish Online
2018-04-12