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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
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
EGAF00008374596 cram 5.1 GB
EGAF00008374597 cram 5.2 GB
EGAF00008374598 cram 5.6 GB
EGAF00008374599 cram 5.8 GB
EGAF00008374600 cram 5.0 GB
EGAF00008374601 cram 4.4 GB
EGAF00008374602 cram 5.5 GB
EGAF00008374603 cram 5.0 GB
EGAF00008377359 cram 11.0 GB
EGAF00008377360 cram 12.3 GB
EGAF00008377361 cram 11.2 GB
EGAF00008377362 cram 11.8 GB
EGAF00008377363 cram 13.5 GB
EGAF00008377364 cram 13.2 GB
EGAF00008377365 cram 15.6 GB
EGAF00008377366 cram 10.9 GB
EGAF00008377367 cram 11.2 GB
EGAF00008377368 cram 9.6 GB
EGAF00008377369 cram 11.7 GB
EGAF00008377370 cram 12.8 GB
EGAF00008377371 cram 11.6 GB
EGAF00008377372 cram 10.7 GB
EGAF00008377373 cram 11.2 GB
EGAF00008377374 cram 12.0 GB
EGAF00008377375 cram 11.1 GB
EGAF00008377376 cram 11.2 GB
EGAF00008377377 cram 9.9 GB
EGAF00008377378 cram 8.2 GB
EGAF00008377379 cram 12.0 GB
EGAF00008377380 cram 8.9 GB
EGAF00008377381 cram 12.6 GB
EGAF00008377382 cram 11.4 GB
EGAF00008377383 cram 11.7 GB
EGAF00008377384 cram 12.9 GB
EGAF00008377385 cram 11.3 GB
EGAF00008377386 cram 9.9 GB
EGAF00008377387 cram 11.1 GB
EGAF00008377388 cram 11.0 GB
EGAF00008377389 cram 10.6 GB
EGAF00008377390 cram 10.7 GB
EGAF00008377391 cram 11.0 GB
EGAF00008377392 cram 12.4 GB
EGAF00008377393 cram 10.2 GB
EGAF00008377394 cram 8.8 GB
EGAF00008377395 cram 9.7 GB
EGAF00008377396 cram 9.8 GB
EGAF00008377397 cram 10.6 GB
EGAF00008377398 cram 9.7 GB
EGAF00008377399 cram 10.1 GB
EGAF00008377400 cram 11.9 GB
EGAF00008377401 cram 11.7 GB
EGAF00008377402 cram 12.6 GB
EGAF00008377403 cram 11.6 GB
EGAF00008377404 cram 11.6 GB
EGAF00008377405 cram 12.2 GB
EGAF00008377406 cram 9.4 GB
EGAF00008377407 cram 12.5 GB
EGAF00008377408 cram 12.5 GB
EGAF00008377409 cram 11.5 GB
EGAF00008377410 cram 13.3 GB
EGAF00008377411 cram 12.8 GB
EGAF00008377412 cram 14.6 GB
EGAF00008377413 cram 13.5 GB
EGAF00008377414 cram 13.4 GB
EGAF00008377415 cram 12.4 GB
EGAF00008377416 cram 14.1 GB
EGAF00008377417 cram 9.8 GB
EGAF00008377418 cram 13.2 GB
EGAF00008377419 cram 13.8 GB
EGAF00008377420 cram 13.0 GB
EGAF00008377421 cram 13.1 GB
EGAF00008377422 cram 12.9 GB
EGAF00008377423 cram 12.8 GB
EGAF00008377424 cram 13.2 GB
EGAF00008377425 cram 12.5 GB
EGAF00008377426 cram 13.5 GB
EGAF00008377427 cram 12.7 GB
EGAF00008377428 cram 12.2 GB
EGAF00008377429 cram 12.5 GB
EGAF00008377430 cram 16.7 GB
EGAF00008377431 cram 13.1 GB
EGAF00008377432 cram 13.7 GB
EGAF00008377433 cram 12.2 GB
EGAF00008377434 cram 13.8 GB
EGAF00008377435 cram 11.5 GB
EGAF00008377436 cram 12.3 GB
EGAF00008377437 cram 12.7 GB
EGAF00008377438 cram 11.4 GB
EGAF00008377439 cram 10.5 GB
EGAF00008377440 cram 13.2 GB
EGAF00008377441 cram 13.0 GB
EGAF00008377442 cram 13.4 GB
EGAF00008377443 cram 13.7 GB
EGAF00008377444 cram 10.8 GB
EGAF00008377445 cram 9.4 GB
EGAF00008377446 cram 13.0 GB
EGAF00008377447 cram 11.3 GB
EGAF00008377448 cram 12.5 GB
EGAF00008377449 cram 11.3 GB
EGAF00008377450 cram 10.2 GB
EGAF00008377451 cram 4.9 GB
EGAF00008377452 cram 5.1 GB
EGAF00008377453 cram 4.4 GB
EGAF00008377454 cram 5.6 GB
EGAF00008377455 cram 4.8 GB
EGAF00008377456 cram 5.5 GB
EGAF00008377457 cram 4.8 GB
EGAF00008377458 cram 5.3 GB
EGAF00008377459 cram 6.0 GB
EGAF00008377460 cram 4.6 GB
EGAF00008377461 cram 4.5 GB
EGAF00008377462 cram 5.6 GB
EGAF00008377463 cram 4.9 GB
EGAF00008377464 cram 4.8 GB
EGAF00008377465 cram 4.9 GB
EGAF00008377466 cram 5.4 GB
EGAF00008377467 cram 9.2 GB
EGAF00008377468 cram 5.0 GB
EGAF00008377469 cram 6.1 GB
EGAF00008377470 cram 4.9 GB
EGAF00008377471 cram 6.7 GB
EGAF00008377472 cram 6.2 GB
EGAF00008377473 cram 9.3 GB
EGAF00008377474 cram 8.5 GB
EGAF00008377475 cram 7.2 GB
EGAF00008377476 cram 6.4 GB
EGAF00008377477 cram 8.9 GB
EGAF00008377478 cram 5.9 GB
EGAF00008377479 cram 6.8 GB
EGAF00008377480 cram 12.2 GB
EGAF00008377481 cram 7.7 GB
EGAF00008377482 cram 6.5 GB
EGAF00008377483 cram 6.8 GB
EGAF00008377484 cram 7.4 GB
EGAF00008377485 cram 6.7 GB
EGAF00008377486 cram 9.3 GB
EGAF00008377487 cram 5.4 GB
EGAF00008377488 cram 6.4 GB
EGAF00008377489 cram 8.8 GB
EGAF00008377490 cram 6.9 GB
EGAF00008377491 cram 6.3 GB
EGAF00008377492 cram 9.4 GB
EGAF00008377493 cram 8.6 GB
EGAF00008377494 cram 7.3 GB
EGAF00008377495 cram 6.5 GB
EGAF00008377496 cram 9.1 GB
EGAF00008377497 cram 6.1 GB
EGAF00008377498 cram 7.0 GB
EGAF00008377499 cram 12.4 GB
EGAF00008377500 cram 7.8 GB
EGAF00008377501 cram 6.6 GB
EGAF00008377502 cram 7.0 GB
EGAF00008377503 cram 7.6 GB
EGAF00008377504 cram 6.9 GB
EGAF00008377505 cram 9.5 GB
EGAF00008377506 cram 5.5 GB
EGAF00008377507 cram 6.5 GB
EGAF00008377508 cram 9.1 GB
EGAF00008377509 cram 3.3 GB
EGAF00008377510 cram 3.4 GB
EGAF00008377511 cram 3.0 GB
EGAF00008377512 cram 3.2 GB
EGAF00008377513 cram 3.7 GB
EGAF00008377514 cram 3.6 GB
EGAF00008377515 cram 4.1 GB
EGAF00008377516 cram 3.0 GB
EGAF00008377517 cram 3.0 GB
EGAF00008377518 cram 2.6 GB
EGAF00008377519 cram 3.2 GB
EGAF00008377520 cram 3.7 GB
EGAF00008377521 cram 3.3 GB
EGAF00008377522 cram 3.4 GB
EGAF00008377523 cram 3.5 GB
EGAF00008377524 cram 3.5 GB
EGAF00008377525 cram 3.3 GB
EGAF00008377526 cram 3.2 GB
EGAF00008377527 cram 2.8 GB
EGAF00008377528 cram 2.3 GB
EGAF00008377529 cram 3.4 GB
EGAF00008377530 cram 2.4 GB
EGAF00008377531 cram 3.5 GB
EGAF00008377532 cram 3.3 GB
EGAF00008377533 cram 3.5 GB
EGAF00008377534 cram 3.8 GB
EGAF00008377535 cram 3.4 GB
EGAF00008377536 cram 2.7 GB
EGAF00008377537 cram 2.9 GB
EGAF00008377538 cram 3.0 GB
EGAF00008377539 cram 2.9 GB
EGAF00008377540 cram 2.9 GB
EGAF00008377541 cram 2.9 GB
EGAF00008377542 cram 3.5 GB
EGAF00008377543 cram 2.6 GB
EGAF00008377544 cram 2.3 GB
EGAF00008377545 cram 2.7 GB
EGAF00008377546 cram 2.6 GB
EGAF00008377547 cram 2.8 GB
EGAF00008377548 cram 2.5 GB
EGAF00008377549 cram 2.7 GB
EGAF00008377550 cram 3.2 GB
EGAF00008377551 cram 3.2 GB
EGAF00008377552 cram 3.5 GB
EGAF00008377553 cram 3.2 GB
EGAF00008377554 cram 3.0 GB
EGAF00008377555 cram 3.2 GB
EGAF00008377556 cram 2.5 GB
EGAF00008377557 cram 3.2 GB
EGAF00008377558 cram 3.2 GB
EGAF00008377559 cram 3.0 GB
EGAF00008377560 cram 3.6 GB
EGAF00008377561 cram 3.4 GB
EGAF00008377562 cram 3.8 GB
EGAF00008377563 cram 3.7 GB
EGAF00008377564 cram 3.6 GB
EGAF00008377565 cram 3.2 GB
EGAF00008377566 cram 3.6 GB
EGAF00008377567 cram 2.7 GB
EGAF00008377568 cram 3.4 GB
EGAF00008377569 cram 3.5 GB
EGAF00008377570 cram 3.4 GB
EGAF00008377571 cram 3.4 GB
EGAF00008377572 cram 3.4 GB
EGAF00008377573 cram 3.3 GB
EGAF00008377574 cram 3.4 GB
EGAF00008377575 cram 3.2 GB
EGAF00008377576 cram 3.6 GB
EGAF00008377577 cram 3.2 GB
EGAF00008377578 cram 3.2 GB
EGAF00008377579 cram 3.2 GB
EGAF00008377580 cram 4.0 GB
EGAF00008377581 cram 3.2 GB
EGAF00008377582 cram 3.5 GB
EGAF00008377583 cram 3.1 GB
EGAF00008377584 cram 3.4 GB
EGAF00008377585 cram 2.9 GB
EGAF00008377586 cram 3.0 GB
EGAF00008377587 cram 3.1 GB
EGAF00008377588 cram 2.9 GB
EGAF00008377589 cram 2.8 GB
EGAF00008377590 cram 3.2 GB
EGAF00008377591 cram 3.3 GB
EGAF00008377592 cram 3.4 GB
EGAF00008377593 cram 3.6 GB
EGAF00008377594 cram 2.7 GB
EGAF00008377595 cram 2.3 GB
EGAF00008377596 cram 3.3 GB
EGAF00008377597 cram 2.9 GB
EGAF00008377598 cram 3.2 GB
EGAF00008377599 cram 2.9 GB
EGAF00008377600 cram 2.5 GB
EGAF00008377601 cram 4.8 GB
EGAF00008377602 cram 5.0 GB
EGAF00008377603 cram 5.3 GB
EGAF00008377604 cram 5.5 GB
EGAF00008377605 cram 5.0 GB
EGAF00008377606 cram 4.4 GB
EGAF00008377607 cram 5.5 GB
EGAF00008377608 cram 4.9 GB
EGAF00008377609 cram 4.8 GB
EGAF00008377610 cram 5.0 GB
EGAF00008377611 cram 4.4 GB
EGAF00008377612 cram 5.3 GB
EGAF00008377613 cram 4.7 GB
EGAF00008377614 cram 5.3 GB
EGAF00008377615 cram 4.7 GB
EGAF00008377616 cram 5.3 GB
EGAF00008377617 cram 6.0 GB
EGAF00008377618 cram 4.6 GB
EGAF00008377619 cram 4.5 GB
EGAF00008377620 cram 5.6 GB
EGAF00008377621 cram 5.0 GB
EGAF00008377622 cram 4.6 GB
EGAF00008377623 cram 4.9 GB
EGAF00008377624 cram 5.4 GB
EGAF00008377625 cram 8.4 GB
EGAF00008377626 cram 4.8 GB
EGAF00008377627 cram 6.0 GB
EGAF00008377628 cram 4.8 GB
EGAF00008377629 cram 4.9 GB
EGAF00008377630 cram 5.1 GB
EGAF00008377631 cram 5.4 GB
EGAF00008377632 cram 5.6 GB
EGAF00008377633 cram 5.0 GB
EGAF00008377634 cram 4.4 GB
EGAF00008377635 cram 5.6 GB
EGAF00008377636 cram 4.9 GB
EGAF00008377637 cram 4.9 GB
EGAF00008377638 cram 5.1 GB
EGAF00008377639 cram 4.4 GB
EGAF00008377640 cram 5.4 GB
EGAF00008377641 cram 4.7 GB
EGAF00008377642 cram 5.4 GB
EGAF00008377643 cram 4.8 GB
EGAF00008377644 cram 5.3 GB
EGAF00008377645 cram 6.0 GB
EGAF00008377646 cram 4.7 GB
EGAF00008377647 cram 4.6 GB
EGAF00008377648 cram 5.6 GB
EGAF00008377649 cram 5.0 GB
EGAF00008377650 cram 4.6 GB
EGAF00008377651 cram 4.9 GB
EGAF00008377652 cram 5.4 GB
EGAF00008377653 cram 8.5 GB
EGAF00008377654 cram 4.8 GB
EGAF00008377655 cram 6.0 GB
EGAF00008377656 cram 4.8 GB
EGAF00008377657 cram 14.3 GB
EGAF00008377658 cram 14.0 GB
EGAF00008377659 cram 15.2 GB
EGAF00008377660 cram 14.0 GB
EGAF00008377661 cram 14.0 GB
EGAF00008377662 cram 13.3 GB
EGAF00008377663 cram 13.4 GB
EGAF00008377664 cram 14.3 GB
EGAF00008377665 cram 13.9 GB
EGAF00008377666 cram 13.7 GB
EGAF00008377667 cram 13.6 GB
EGAF00008377668 cram 13.6 GB
EGAF00008377669 cram 14.1 GB
EGAF00008377670 cram 13.9 GB
EGAF00008377671 cram 13.2 GB
EGAF00008377672 cram 13.0 GB
EGAF00008377673 cram 13.5 GB
EGAF00008377674 cram 13.5 GB
EGAF00008377675 cram 14.1 GB
EGAF00008377676 cram 14.5 GB
EGAF00008377677 cram 13.1 GB
EGAF00008377678 cram 15.0 GB
EGAF00008377679 cram 15.1 GB
EGAF00008377680 cram 13.7 GB
EGAF00008377681 cram 14.1 GB
EGAF00008377682 cram 16.1 GB
EGAF00008377683 cram 16.3 GB
EGAF00008377684 cram 14.4 GB
EGAF00008377685 cram 15.5 GB
EGAF00008377686 cram 15.1 GB
EGAF00008377687 cram 12.4 GB
EGAF00008377688 cram 13.0 GB
EGAF00008377689 cram 15.0 GB
EGAF00008377690 cram 12.7 GB
EGAF00008377691 cram 13.6 GB
EGAF00008377692 cram 32.6 GB
EGAF00008377693 cram 16.8 GB
EGAF00008377694 cram 15.9 GB
EGAF00008377695 cram 14.3 GB
EGAF00008377696 cram 14.3 GB
EGAF00008377697 cram 14.9 GB
EGAF00008377698 cram 3.6 GB
EGAF00008377699 cram 3.5 GB
EGAF00008377700 cram 3.7 GB
EGAF00008377701 cram 3.5 GB
EGAF00008377702 cram 3.4 GB
EGAF00008377703 cram 3.2 GB
EGAF00008377704 cram 3.2 GB
EGAF00008377705 cram 3.5 GB
EGAF00008377706 cram 3.4 GB
EGAF00008377707 cram 3.4 GB
EGAF00008377708 cram 3.3 GB
EGAF00008377709 cram 3.3 GB
EGAF00008377710 cram 3.4 GB
EGAF00008377711 cram 3.4 GB
EGAF00008377712 cram 3.2 GB
EGAF00008377713 cram 3.2 GB
EGAF00008377714 cram 3.3 GB
EGAF00008377715 cram 3.3 GB
EGAF00008377716 cram 3.5 GB
EGAF00008377717 cram 3.8 GB
EGAF00008377718 cram 3.3 GB
EGAF00008377719 cram 3.7 GB
EGAF00008377720 cram 3.9 GB
EGAF00008377721 cram 3.4 GB
EGAF00008377722 cram 3.5 GB
EGAF00008377723 cram 4.1 GB
EGAF00008377724 cram 4.1 GB
EGAF00008377725 cram 3.7 GB
EGAF00008377726 cram 4.0 GB
EGAF00008377727 cram 3.9 GB
EGAF00008377728 cram 3.1 GB
EGAF00008377729 cram 3.2 GB
EGAF00008377730 cram 3.5 GB
EGAF00008377731 cram 3.4 GB
EGAF00008377732 cram 3.4 GB
EGAF00008377733 cram 7.9 GB
EGAF00008377734 cram 4.5 GB
EGAF00008377735 cram 4.1 GB
EGAF00008377736 cram 3.6 GB
EGAF00008377737 cram 3.6 GB
EGAF00008377738 cram 3.6 GB
388 Files (2.9 TB)