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Timing the landmark events in the evolution of clear cell renal cell cancer

Clear cell renal cancer is characterized by near-universal loss of the short arm of chromosome 3 (3p). This event arises through unknown mechanisms, but critically results in the loss of several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cancer (ccRCC) recruited into the Renal TRACERx study. We find novel hotspots of point mutations in the 5'-UTR of TERT, targeting a MYC-MAX repressor, that result in telomere lengthening. The most common structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. Using molecular clocks, we estimate this occurs in childhood or adolescence, generally preceding emergence of the most recent common ancestor by years to decades. Similar genomic changes recent common ancestor by years to decades. Similar genomic changes are seen in inherited kidney cancers. 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. Targeting essential genes in deleted regions of chromosome 3p could represent a potential preventative strategy for renal cancer.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001000934 Cancer Genomics

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00000787918 cram 36.5 GB
EGAF00000787919 cram 40.2 GB
EGAF00000787920 cram 39.4 GB
EGAF00000787921 cram 40.5 GB
EGAF00000787922 cram 39.8 GB
EGAF00000787923 cram 40.1 GB
EGAF00000787924 cram 39.5 GB
EGAF00000787925 cram 37.5 GB
EGAF00000787926 cram 38.3 GB
EGAF00000787927 cram 39.0 GB
EGAF00000787928 cram 38.5 GB
EGAF00000787929 cram 39.3 GB
EGAF00000787930 cram 38.2 GB
EGAF00000787931 cram 38.2 GB
EGAF00000787932 cram 37.3 GB
EGAF00000787933 cram 42.0 GB
EGAF00000787934 cram 42.3 GB
EGAF00000787935 cram 43.1 GB
EGAF00000787936 cram 41.9 GB
EGAF00000787937 cram 42.4 GB
EGAF00000787938 cram 40.6 GB
EGAF00000787939 cram 40.2 GB
EGAF00000787940 cram 38.6 GB
EGAF00000787941 cram 39.7 GB
EGAF00000787942 cram 39.8 GB
EGAF00000787943 cram 39.5 GB
EGAF00000787944 cram 39.5 GB
EGAF00000787945 cram 39.3 GB
EGAF00000787946 cram 39.9 GB
EGAF00000787947 cram 38.8 GB
EGAF00000787948 cram 37.0 GB
EGAF00000787949 cram 37.8 GB
EGAF00000787950 cram 42.6 GB
EGAF00000787951 cram 43.0 GB
EGAF00000787952 cram 44.2 GB
EGAF00000787953 cram 43.2 GB
EGAF00000787954 cram 43.5 GB
EGAF00000787955 cram 42.2 GB
EGAF00000787956 cram 42.4 GB
EGAF00000787957 cram 48.7 GB
EGAF00000787958 cram 48.3 GB
EGAF00000787959 cram 49.5 GB
EGAF00000787960 cram 47.8 GB
EGAF00000787961 cram 48.8 GB
EGAF00000787962 cram 49.2 GB
EGAF00000787963 cram 48.9 GB
EGAF00000787964 cram 45.9 GB
EGAF00000787965 cram 45.3 GB
EGAF00000787966 cram 46.9 GB
EGAF00000787967 cram 45.6 GB
EGAF00000787968 cram 46.7 GB
EGAF00000787969 cram 45.8 GB
EGAF00000787970 cram 45.6 GB
EGAF00000787971 cram 45.6 GB
EGAF00000787972 cram 47.0 GB
EGAF00000787973 cram 43.8 GB
EGAF00000787974 cram 43.2 GB
EGAF00000787975 cram 42.3 GB
EGAF00000787976 cram 41.8 GB
EGAF00000787977 cram 42.0 GB
EGAF00000787978 cram 42.7 GB
EGAF00000787979 cram 43.2 GB
EGAF00000787980 cram 41.1 GB
EGAF00000787981 cram 47.3 GB
EGAF00000787982 cram 41.5 GB
EGAF00000787983 cram 46.7 GB
EGAF00000787984 cram 45.9 GB
EGAF00000787985 cram 45.0 GB
EGAF00000787986 cram 44.6 GB
EGAF00000787987 cram 44.3 GB
EGAF00000787988 cram 41.8 GB
EGAF00000787989 cram 47.7 GB
EGAF00000787990 cram 46.5 GB
EGAF00000787991 cram 45.9 GB
EGAF00000787992 cram 46.4 GB
EGAF00000787993 cram 47.8 GB
EGAF00000787994 cram 46.2 GB
EGAF00000787995 cram 45.4 GB
EGAF00000787996 cram 48.3 GB
EGAF00000787997 cram 49.2 GB
EGAF00000787998 cram 47.8 GB
EGAF00000787999 cram 49.4 GB
EGAF00000788000 cram 50.0 GB
EGAF00000788001 cram 50.8 GB
EGAF00000788002 cram 47.3 GB
EGAF00000788003 cram 42.7 GB
EGAF00000788004 cram 45.1 GB
EGAF00000788005 cram 46.4 GB
EGAF00000788006 cram 44.6 GB
EGAF00000788007 cram 46.2 GB
EGAF00000788008 cram 45.0 GB
EGAF00000788009 cram 42.2 GB
EGAF00000788011 cram 41.8 GB
EGAF00000788012 cram 44.2 GB
EGAF00000788013 cram 44.2 GB
EGAF00000788014 cram 42.6 GB
EGAF00000788015 cram 47.7 GB
EGAF00000788016 cram 47.1 GB
EGAF00000788017 cram 46.2 GB
EGAF00000788018 cram 43.8 GB
EGAF00000788019 cram 47.6 GB
EGAF00000788020 cram 44.5 GB
EGAF00000788021 cram 49.7 GB
EGAF00000788023 cram 45.0 GB
EGAF00000788024 cram 49.1 GB
EGAF00000788025 cram 52.9 GB
EGAF00000788026 cram 52.5 GB
EGAF00000788027 cram 40.9 GB
EGAF00000788028 cram 36.1 GB
EGAF00000788029 cram 43.6 GB
EGAF00000788030 cram 46.1 GB
EGAF00000788031 cram 45.7 GB
EGAF00000788032 cram 47.3 GB
EGAF00000788033 cram 41.9 GB
EGAF00000788034 cram 41.9 GB
EGAF00000788035 cram 42.0 GB
EGAF00000788036 cram 42.3 GB
EGAF00000788037 cram 42.0 GB
EGAF00000788038 cram 41.7 GB
EGAF00000788039 cram 41.2 GB
EGAF00000788040 cram 40.7 GB
EGAF00000788041 cram 43.0 GB
EGAF00000788042 cram 43.6 GB
EGAF00000788043 cram 42.6 GB
EGAF00000788044 cram 42.8 GB
EGAF00000788045 cram 42.5 GB
EGAF00000788046 cram 41.8 GB
EGAF00000788047 cram 41.4 GB
EGAF00000788048 cram 43.0 GB
EGAF00000788049 cram 42.8 GB
EGAF00000788050 cram 44.3 GB
EGAF00000788051 cram 43.8 GB
EGAF00000788052 cram 42.8 GB
EGAF00000788053 cram 41.7 GB
EGAF00000788054 cram 41.4 GB
EGAF00000788055 cram 41.8 GB
EGAF00000788056 cram 40.9 GB
EGAF00000788057 cram 41.6 GB
EGAF00000788058 cram 41.0 GB
EGAF00000788059 cram 41.2 GB
EGAF00000788060 cram 40.9 GB
EGAF00000788061 cram 41.0 GB
EGAF00000788062 cram 42.8 GB
EGAF00000788063 cram 41.0 GB
EGAF00000788064 cram 40.0 GB
EGAF00000788065 cram 43.5 GB
EGAF00000788066 cram 43.2 GB
EGAF00000788067 cram 46.5 GB
EGAF00000788068 cram 46.7 GB
EGAF00000788069 cram 48.5 GB
EGAF00000788070 cram 47.2 GB
EGAF00000788071 cram 45.9 GB
EGAF00000788072 cram 44.3 GB
EGAF00000788073 cram 42.9 GB
EGAF00000788074 cram 43.3 GB
EGAF00000788075 cram 43.7 GB
EGAF00000788076 cram 43.8 GB
EGAF00000788077 cram 42.3 GB
EGAF00000788078 cram 42.9 GB
EGAF00000788079 cram 43.2 GB
EGAF00000788080 cram 41.3 GB
EGAF00000788081 cram 48.9 GB
EGAF00000788082 cram 49.7 GB
EGAF00000788083 cram 49.5 GB
EGAF00000788084 cram 47.8 GB
EGAF00000788085 cram 49.2 GB
EGAF00000788086 cram 42.0 GB
EGAF00000788087 cram 42.9 GB
EGAF00000788088 cram 43.2 GB
EGAF00000788089 cram 43.1 GB
EGAF00000788090 cram 43.1 GB
EGAF00000788091 cram 44.8 GB
EGAF00000788092 cram 42.7 GB
EGAF00000788093 cram 49.7 GB
EGAF00000788094 cram 46.9 GB
EGAF00000788095 cram 45.0 GB
EGAF00000788096 cram 42.3 GB
EGAF00000790664 cram 39.9 GB
EGAF00000790665 cram 40.3 GB
EGAF00000790666 cram 40.6 GB
EGAF00000790667 cram 40.7 GB
EGAF00000790668 cram 40.8 GB
EGAF00000790669 cram 43.0 GB
EGAF00000790670 cram 40.0 GB
EGAF00000790671 cram 41.0 GB
EGAF00000790672 cram 41.2 GB
EGAF00000790673 cram 42.4 GB
EGAF00000790674 cram 42.0 GB
EGAF00000790675 cram 44.8 GB
EGAF00000790676 cram 40.6 GB
EGAF00000790677 cram 39.8 GB
EGAF00000790678 cram 41.1 GB
EGAF00000790679 cram 39.9 GB
EGAF00000790680 cram 39.8 GB
EGAF00000790681 cram 37.6 GB
EGAF00000790682 cram 40.2 GB
EGAF00000790683 cram 37.6 GB
EGAF00000790684 cram 39.1 GB
EGAF00000790738 cram 38.5 GB
EGAF00000790739 cram 39.8 GB
EGAF00000790740 cram 38.5 GB
EGAF00000790741 cram 41.7 GB
EGAF00000790742 cram 42.3 GB
EGAF00000790866 cram 42.7 GB
EGAF00000790867 cram 40.7 GB
EGAF00000790868 cram 43.1 GB
EGAF00000790869 cram 45.7 GB
EGAF00000790870 cram 42.2 GB
EGAF00000790871 cram 46.4 GB
EGAF00000790872 cram 48.7 GB
EGAF00000790873 cram 48.3 GB
EGAF00000790874 cram 45.6 GB
EGAF00000790875 cram 46.1 GB
EGAF00000790876 cram 45.0 GB
EGAF00000790877 cram 42.2 GB
EGAF00000790878 cram 42.6 GB
EGAF00000790879 cram 43.3 GB
EGAF00000790880 cram 41.3 GB
EGAF00000790881 cram 41.7 GB
EGAF00000790882 cram 34.7 GB
EGAF00000790883 cram 38.6 GB
EGAF00000790884 cram 39.4 GB
EGAF00000790885 cram 39.4 GB
EGAF00000790886 cram 40.0 GB
EGAF00000790887 cram 38.2 GB
EGAF00000790942 cram 39.3 GB
EGAF00000790943 cram 38.5 GB
EGAF00000790944 cram 39.0 GB
EGAF00000790945 cram 38.7 GB
EGAF00000790946 cram 39.9 GB
EGAF00000790947 cram 35.9 GB
EGAF00000790948 cram 45.0 GB
EGAF00000790949 cram 46.2 GB
EGAF00000790950 cram 47.7 GB
EGAF00000790951 cram 45.1 GB
EGAF00000790952 cram 46.3 GB
EGAF00000790953 cram 44.8 GB
EGAF00000790954 cram 44.6 GB
EGAF00000790955 cram 44.7 GB
EGAF00000790956 cram 44.6 GB
EGAF00000790957 cram 45.8 GB
EGAF00000790958 cram 46.1 GB
EGAF00000790959 cram 45.7 GB
EGAF00000790960 cram 44.6 GB
EGAF00000790961 cram 45.5 GB
EGAF00000790962 cram 45.8 GB
EGAF00000790963 cram 43.7 GB
EGAF00000790964 cram 43.1 GB
EGAF00000790965 cram 44.9 GB
EGAF00000790966 cram 44.7 GB
EGAF00000790967 cram 43.6 GB
EGAF00000790968 cram 43.8 GB
EGAF00000792284 cram 42.2 GB
EGAF00000792285 cram 46.4 GB
EGAF00000798051 cram 43.6 GB
EGAF00000798052 cram 45.0 GB
EGAF00000798053 cram 42.0 GB
EGAF00000798054 cram 42.3 GB
EGAF00000798055 cram 43.3 GB
EGAF00000798056 cram 41.0 GB
EGAF00000798057 cram 43.0 GB
EGAF00000798058 cram 46.1 GB
EGAF00000798059 cram 47.3 GB
EGAF00000798060 cram 46.9 GB
EGAF00000798061 cram 45.3 GB
EGAF00000798062 cram 43.5 GB
EGAF00000798063 cram 43.4 GB
EGAF00000798064 cram 43.1 GB
EGAF00000798065 cram 43.6 GB
EGAF00000834521 cram 43.3 GB
EGAF00000834522 cram 43.3 GB
EGAF00000834523 cram 43.7 GB
EGAF00000834524 cram 34.9 GB
EGAF00000834525 cram 39.5 GB
EGAF00000834526 cram 41.6 GB
EGAF00000834527 cram 40.6 GB
EGAF00000834528 cram 38.9 GB
EGAF00000834529 cram 40.9 GB
EGAF00000834530 cram 42.1 GB
EGAF00000834531 cram 40.3 GB
EGAF00000834532 cram 40.2 GB
EGAF00000834533 cram 41.8 GB
EGAF00000834534 cram 45.1 GB
EGAF00000834535 cram 44.4 GB
EGAF00000834536 cram 43.2 GB
EGAF00000834537 cram 41.5 GB
EGAF00000834538 cram 47.0 GB
EGAF00000834539 cram 44.2 GB
EGAF00000834540 cram 43.8 GB
EGAF00000834541 cram 39.8 GB
EGAF00001008034 cram 37.8 GB
EGAF00001701906 cram 48.5 GB
292 Files (12.6 TB)