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Somatic mutant selection is altered by prior NOTCH1 mutation in ageing esophageal epithelium

Authors: Charlotte King1, Emilie Abbie1, Joanna C. Fowler1, Irina Abnizova1, Roshan K. Sood1, Swee Hoe Ong1, Michael W. J. Hall1,2, Faye Lynch-Williams3, Benjamin A. Hall4, Philip H. Jones1,2,5 Abstract: In cancer evolution, genome alterations often occur in a specific order, implying selection depends on the prior clonal genotype 1-3. It is unknown if similar constraints operate in normal epithelia. Here, we mapped mutations in normal mid-esophagus of aged UK subjects. Mutant NOTCH1 clones colonized most of the epithelium by age 60 and above 70 tissue was saturated with mutants under strong competitive selection. Mutant TP53 was more strongly selected in donors over 60 years of age. Samples predominantly mutant for NOTCH1 showed increased selection of NOTCH2 mutants and weaker selection of mutant TP53 compared with samples that were mostly NOTCH1 wild type. In mouse esophagus lacking Notch1 we observed strong selection of mutant Notch2 and other genes not selected in wild type esophagus. In normal ageing esophagus, the first driver mutation may change the trajectory of subsequent somatic evolution by altering mutant selection.

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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
EGAS00001001933 Other
EGAS00001002416 Cancer Genomics
EGAS00001007696 Other

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
EGAF00002025476 cram 9.0 GB
EGAF00002025477 cram 6.4 GB
EGAF00002025478 cram 8.5 GB
EGAF00002025563 cram 10.4 GB
EGAF00002025564 cram 9.1 GB
EGAF00002025565 cram 6.4 GB
EGAF00002025566 cram 8.5 GB
EGAF00002025567 cram 10.4 GB
EGAF00002025568 cram 9.1 GB
EGAF00002025569 cram 6.5 GB
EGAF00002025570 cram 8.5 GB
EGAF00002025571 cram 10.6 GB
EGAF00002025572 cram 9.2 GB
EGAF00002025573 cram 6.5 GB
EGAF00002025574 cram 8.6 GB
EGAF00002025575 cram 10.4 GB
EGAF00008373367 cram 32.4 GB
EGAF00008373951 cram 7.1 GB
EGAF00008373952 cram 6.7 GB
EGAF00008373956 cram 7.4 GB
EGAF00008373957 cram 7.0 GB
EGAF00008373961 cram 7.2 GB
EGAF00008373962 cram 6.9 GB
EGAF00008373966 cram 7.1 GB
EGAF00008373967 cram 6.7 GB
EGAF00008373971 cram 6.9 GB
EGAF00008373972 cram 6.6 GB
EGAF00008373976 cram 7.0 GB
EGAF00008373977 cram 6.7 GB
EGAF00008373983 cram 5.4 GB
EGAF00008373984 cram 5.5 GB
EGAF00008373989 cram 5.6 GB
EGAF00008373990 cram 5.6 GB
EGAF00008373995 cram 5.4 GB
EGAF00008373996 cram 5.4 GB
EGAF00008374001 cram 5.3 GB
EGAF00008374002 cram 5.4 GB
EGAF00008374007 cram 5.4 GB
EGAF00008374008 cram 5.5 GB
EGAF00008374013 cram 5.4 GB
EGAF00008374014 cram 5.5 GB
EGAF00008374019 cram 5.5 GB
EGAF00008374020 cram 5.6 GB
EGAF00008374025 cram 5.5 GB
EGAF00008374026 cram 5.5 GB
EGAF00008374029 cram 5.0 GB
EGAF00008374035 cram 5.2 GB
EGAF00008374041 cram 5.1 GB
EGAF00008374047 cram 5.0 GB
EGAF00008374053 cram 5.1 GB
EGAF00008374059 cram 5.1 GB
EGAF00008374065 cram 6.5 GB
EGAF00008374066 cram 6.3 GB
EGAF00008374070 cram 6.4 GB
EGAF00008374071 cram 6.2 GB
EGAF00008374075 cram 5.5 GB
EGAF00008374081 cram 5.4 GB
EGAF00008374089 cram 5.4 GB
EGAF00008374095 cram 5.4 GB
EGAF00008374101 cram 5.4 GB
EGAF00008374107 cram 5.4 GB
EGAF00008374113 cram 5.4 GB
EGAF00008374119 cram 5.3 GB
EGAF00008374125 cram 5.3 GB
EGAF00008374131 cram 5.1 GB
EGAF00008377365 cram 15.6 GB
EGAF00008377430 cram 16.7 GB
EGAF00008377456 cram 5.5 GB
EGAF00008377457 cram 4.8 GB
EGAF00008377473 cram 9.3 GB
EGAF00008377481 cram 7.7 GB
EGAF00008377492 cram 9.4 GB
EGAF00008377500 cram 7.8 GB
EGAF00008377515 cram 4.1 GB
EGAF00008377580 cram 4.0 GB
EGAF00008377614 cram 5.3 GB
EGAF00008377615 cram 4.7 GB
EGAF00008377642 cram 5.4 GB
EGAF00008377643 cram 4.8 GB
EGAF00008377692 cram 32.6 GB
EGAF00008377733 cram 7.9 GB
EGAF00008377739 cram 19.4 GB
EGAF00008377740 cram 22.8 GB
EGAF00008377741 cram 24.2 GB
EGAF00008377742 cram 22.8 GB
EGAF00008377743 cram 28.4 GB
EGAF00008377744 cram 23.8 GB
EGAF00008377745 cram 22.6 GB
EGAF00008377746 cram 23.3 GB
EGAF00008377747 cram 27.9 GB
EGAF00008377748 cram 19.9 GB
EGAF00008377749 cram 26.0 GB
EGAF00008377750 cram 17.1 GB
EGAF00008377751 cram 13.1 GB
94 Files (887.1 GB)