dc.contributor.author | Mitchell, TJ | |
dc.contributor.author | Turajlic, S | |
dc.contributor.author | Rowan, A | |
dc.contributor.author | Nicol, D | |
dc.contributor.author | Farmery, JHR | |
dc.contributor.author | O'Brien, T | |
dc.contributor.author | Martincorena, I | |
dc.contributor.author | Tarpey, P | |
dc.contributor.author | Angelopoulos, N | |
dc.contributor.author | Yates, LR | |
dc.contributor.author | Butler, AP | |
dc.contributor.author | Raine, K | |
dc.contributor.author | Stewart, GD | |
dc.contributor.author | Challacombe, B | |
dc.contributor.author | Fernando, A | |
dc.contributor.author | Lopez, JI | |
dc.contributor.author | Hazell, S | |
dc.contributor.author | Chandra, A | |
dc.contributor.author | Chowdhury, S | |
dc.contributor.author | Rudman, S | |
dc.contributor.author | Soultati, A | |
dc.contributor.author | Stamp, G | |
dc.contributor.author | Fotiadis, N | |
dc.contributor.author | Pickering, L | |
dc.contributor.author | Au, L | |
dc.contributor.author | Spain, L | |
dc.contributor.author | Lynch, J | |
dc.contributor.author | Stares, M | |
dc.contributor.author | Teague, J | |
dc.contributor.author | Maura, F | |
dc.contributor.author | Wedge, DC | |
dc.contributor.author | Horswell, S | |
dc.contributor.author | Chambers, T | |
dc.contributor.author | Litchfield, K | |
dc.contributor.author | Xu, H | |
dc.contributor.author | Stewart, A | |
dc.contributor.author | Elaidi, R | |
dc.contributor.author | Oudard, S | |
dc.contributor.author | McGranahan, N | |
dc.contributor.author | Csabai, I | |
dc.contributor.author | Gore, M | |
dc.contributor.author | Futreal, PA | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Lynch, AG | |
dc.contributor.author | Szallasi, Z | |
dc.contributor.author | Swanton, C | |
dc.contributor.author | Campbell, PJ | |
dc.contributor.author | TRACERx Renal Consortium, | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-08-30T09:52:21Z | |
dc.date.available | 2022-08-30T09:52:21Z | |
dc.date.issued | 2018-04-19 | |
dc.identifier | S0092-8674(18)30164-8 | |
dc.identifier.citation | Cell, 2018, 173 (3), pp. 611 - 623.e17 | |
dc.identifier.issn | 0092-8674 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5345 | |
dc.identifier.eissn | 1097-4172 | |
dc.identifier.eissn | 1097-4172 | |
dc.identifier.doi | 10.1016/j.cell.2018.02.020 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 611 - 623.e17 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.relation.ispartof | Cell | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | cancer evolution | |
dc.subject | chromothripsis | |
dc.subject | clear cell renal cell carcinoma | |
dc.subject | 5' Untranslated Regions | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Carcinoma, Renal Cell | |
dc.subject | Chromosomes, Human, Pair 3 | |
dc.subject | Chromosomes, Human, Pair 5 | |
dc.subject | Disease Progression | |
dc.subject | Female | |
dc.subject | Gene Dosage | |
dc.subject | Genome, Human | |
dc.subject | Humans | |
dc.subject | Kidney Neoplasms | |
dc.subject | Male | |
dc.subject | Middle Aged | |
dc.subject | Mutation | |
dc.subject | Prospective Studies | |
dc.subject | Telomerase | |
dc.subject | Von Hippel-Lindau Tumor Suppressor Protein | |
dc.title | Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-02-07 | |
dc.date.updated | 2022-08-30T09:51:30Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.cell.2018.02.020 | |
rioxxterms.licenseref.startdate | 2018-04-19 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29656891 | |
pubs.issue | 3 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Experimental Pathology | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.) | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/17/18 Starting Cohort | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.cell.2018.02.020 | |
pubs.volume | 173 | |
icr.researchteam | Experimental Pathology | |
icr.researchteam | Melanoma & Kidney Cancer | |
icr.researchteam | RMH Honorary Faculty | |
dc.contributor.icrauthor | Au, Lewis | |
dc.contributor.icrauthor | Spain, Lavinia | |
icr.provenance | Deposited by Mr Arek Surman on 2022-08-30. Deposit type is initial. No. of files: 1. Files: Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer TRACERx Renal.pdf | |