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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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Study ID Study Title Study Type
EGAS00001004462 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
EGAF00008374134 cram 440.0 MB
EGAF00008374135 cram 422.0 MB
EGAF00008374136 cram 395.1 MB
EGAF00008374137 cram 398.5 MB
EGAF00008374138 cram 396.5 MB
EGAF00008374139 cram 394.2 MB
EGAF00008374140 cram 407.6 MB
EGAF00008374141 cram 384.1 MB
EGAF00008374142 cram 380.9 MB
EGAF00008374143 cram 389.8 MB
EGAF00008374144 cram 360.1 MB
EGAF00008374145 cram 404.9 MB
EGAF00008374146 cram 365.9 MB
EGAF00008374147 cram 369.4 MB
EGAF00008374148 cram 350.7 MB
EGAF00008374149 cram 347.4 MB
EGAF00008374150 cram 328.7 MB
EGAF00008374151 cram 427.2 MB
EGAF00008374152 cram 401.0 MB
EGAF00008374153 cram 335.1 MB
EGAF00008374154 cram 466.2 MB
EGAF00008374155 cram 388.3 MB
EGAF00008374156 cram 404.2 MB
EGAF00008374157 cram 375.1 MB
EGAF00008374158 cram 386.1 MB
EGAF00008374159 cram 351.1 MB
EGAF00008374160 cram 425.6 MB
EGAF00008374161 cram 426.5 MB
EGAF00008374162 cram 417.6 MB
EGAF00008374163 cram 426.2 MB
EGAF00008374164 cram 394.6 MB
EGAF00008374165 cram 411.0 MB
EGAF00008374166 cram 325.3 MB
EGAF00008374167 cram 364.1 MB
EGAF00008374168 cram 353.6 MB
EGAF00008374169 cram 405.5 MB
EGAF00008374170 cram 398.7 MB
EGAF00008374171 cram 368.9 MB
EGAF00008374172 cram 400.0 MB
EGAF00008374173 cram 374.1 MB
EGAF00008374174 cram 372.4 MB
EGAF00008374175 cram 361.4 MB
EGAF00008374176 cram 294.7 MB
EGAF00008374177 cram 368.2 MB
EGAF00008374178 cram 342.1 MB
EGAF00008374179 cram 289.5 MB
EGAF00008374180 cram 375.3 MB
EGAF00008374181 cram 373.5 MB
EGAF00008374182 cram 310.5 MB
EGAF00008374183 cram 390.3 MB
EGAF00008374184 cram 396.5 MB
EGAF00008374185 cram 368.6 MB
EGAF00008374186 cram 339.9 MB
EGAF00008374187 cram 364.9 MB
EGAF00008374188 cram 336.3 MB
EGAF00008374189 cram 362.2 MB
EGAF00008374190 cram 398.9 MB
EGAF00008374191 cram 387.0 MB
EGAF00008374192 cram 348.6 MB
EGAF00008374193 cram 373.9 MB
EGAF00008374194 cram 352.6 MB
EGAF00008374195 cram 344.1 MB
EGAF00008374196 cram 361.5 MB
EGAF00008374197 cram 367.2 MB
EGAF00008374198 cram 338.6 MB
EGAF00008374199 cram 369.5 MB
EGAF00008374200 cram 367.8 MB
EGAF00008374201 cram 334.0 MB
EGAF00008374202 cram 384.8 MB
EGAF00008374203 cram 365.6 MB
EGAF00008374204 cram 330.8 MB
EGAF00008374205 cram 382.3 MB
EGAF00008374206 cram 430.2 MB
EGAF00008374207 cram 427.8 MB
EGAF00008374208 cram 356.5 MB
EGAF00008374209 cram 341.2 MB
EGAF00008374210 cram 407.3 MB
EGAF00008374211 cram 391.8 MB
EGAF00008374212 cram 405.2 MB
EGAF00008374213 cram 400.1 MB
EGAF00008374214 cram 380.0 MB
EGAF00008374215 cram 484.7 MB
EGAF00008374216 cram 366.5 MB
EGAF00008374217 cram 359.7 MB
EGAF00008374218 cram 427.8 MB
EGAF00008374219 cram 396.7 MB
EGAF00008374220 cram 404.3 MB
EGAF00008374221 cram 497.1 MB
EGAF00008374222 cram 397.0 MB
EGAF00008374223 cram 597.4 MB
EGAF00008374224 cram 351.1 MB
EGAF00008374225 cram 366.5 MB
EGAF00008374226 cram 362.6 MB
EGAF00008374227 cram 349.4 MB
EGAF00008374228 cram 338.3 MB
EGAF00008374229 cram 359.9 MB
EGAF00008374230 cram 397.1 MB
EGAF00008374231 cram 403.8 MB
EGAF00008374232 cram 395.6 MB
EGAF00008374233 cram 396.4 MB
EGAF00008374234 cram 455.1 MB
EGAF00008374235 cram 394.2 MB
EGAF00008374236 cram 434.7 MB
EGAF00008374237 cram 440.3 MB
EGAF00008374238 cram 338.8 MB
EGAF00008374239 cram 325.0 MB
EGAF00008374240 cram 356.2 MB
EGAF00008374241 cram 408.5 MB
EGAF00008374242 cram 393.3 MB
EGAF00008374243 cram 349.4 MB
EGAF00008374244 cram 376.8 MB
EGAF00008374245 cram 395.9 MB
EGAF00008374246 cram 401.0 MB
EGAF00008374247 cram 367.2 MB
EGAF00008374248 cram 389.3 MB
EGAF00008374249 cram 359.1 MB
EGAF00008374250 cram 381.6 MB
EGAF00008374251 cram 364.4 MB
EGAF00008374252 cram 314.1 MB
EGAF00008374253 cram 400.0 MB
EGAF00008374254 cram 402.9 MB
EGAF00008374255 cram 629.5 MB
EGAF00008374256 cram 402.6 MB
EGAF00008374257 cram 387.3 MB
EGAF00008374258 cram 378.1 MB
EGAF00008374259 cram 386.9 MB
EGAF00008374260 cram 417.8 MB
EGAF00008374261 cram 422.4 MB
EGAF00008374262 cram 350.9 MB
EGAF00008374263 cram 309.8 MB
EGAF00008374264 cram 309.9 MB
EGAF00008374265 cram 341.4 MB
EGAF00008374266 cram 361.1 MB
EGAF00008374267 cram 359.1 MB
EGAF00008374268 cram 359.0 MB
EGAF00008374269 cram 353.3 MB
EGAF00008374270 cram 413.6 MB
EGAF00008374271 cram 324.2 MB
EGAF00008374272 cram 334.7 MB
EGAF00008374273 cram 320.8 MB
EGAF00008374274 cram 341.5 MB
EGAF00008374275 cram 355.8 MB
EGAF00008374276 cram 370.8 MB
EGAF00008374277 cram 362.9 MB
EGAF00008374278 cram 381.5 MB
EGAF00008374279 cram 386.9 MB
EGAF00008374280 cram 354.9 MB
EGAF00008374281 cram 340.6 MB
EGAF00008374282 cram 336.1 MB
EGAF00008374283 cram 353.9 MB
EGAF00008374284 cram 306.5 MB
EGAF00008374285 cram 367.2 MB
EGAF00008374286 cram 385.0 MB
EGAF00008374287 cram 450.4 MB
EGAF00008374288 cram 322.5 MB
EGAF00008374289 cram 350.0 MB
EGAF00008374290 cram 322.0 MB
EGAF00008374291 cram 349.4 MB
EGAF00008374292 cram 328.4 MB
EGAF00008374293 cram 362.6 MB
EGAF00008374294 cram 372.5 MB
EGAF00008374295 cram 351.6 MB
EGAF00008374296 cram 364.9 MB
EGAF00008374297 cram 347.2 MB
EGAF00008374298 cram 364.2 MB
EGAF00008374299 cram 378.7 MB
EGAF00008374300 cram 375.4 MB
EGAF00008374301 cram 381.4 MB
EGAF00008374302 cram 398.4 MB
EGAF00008374303 cram 377.3 MB
EGAF00008374304 cram 415.6 MB
EGAF00008374305 cram 348.2 MB
EGAF00008374306 cram 407.9 MB
EGAF00008374307 cram 408.7 MB
EGAF00008374308 cram 411.8 MB
EGAF00008374309 cram 438.2 MB
EGAF00008374310 cram 429.3 MB
EGAF00008374311 cram 356.8 MB
EGAF00008374312 cram 380.5 MB
EGAF00008374313 cram 377.3 MB
EGAF00008374314 cram 401.3 MB
EGAF00008374315 cram 384.7 MB
EGAF00008374316 cram 377.7 MB
EGAF00008374317 cram 421.8 MB
EGAF00008374318 cram 528.9 MB
EGAF00008374319 cram 366.9 MB
EGAF00008374320 cram 364.7 MB
EGAF00008374321 cram 354.1 MB
EGAF00008374322 cram 375.2 MB
EGAF00008374323 cram 365.5 MB
EGAF00008374324 cram 387.2 MB
EGAF00008374325 cram 260.3 MB
EGAF00008374326 cram 268.4 MB
EGAF00008374327 cram 258.7 MB
EGAF00008374328 cram 262.8 MB
EGAF00008374329 cram 264.8 MB
EGAF00008374330 cram 248.4 MB
EGAF00008374331 cram 268.2 MB
EGAF00008374332 cram 265.0 MB
EGAF00008374333 cram 303.1 MB
EGAF00008374334 cram 285.9 MB
EGAF00008374335 cram 290.0 MB
EGAF00008374336 cram 259.0 MB
EGAF00008374337 cram 294.4 MB
EGAF00008374338 cram 283.5 MB
EGAF00008374339 cram 296.5 MB
EGAF00008374340 cram 289.6 MB
EGAF00008374341 cram 293.3 MB
EGAF00008374342 cram 318.3 MB
EGAF00008374343 cram 301.7 MB
EGAF00008374344 cram 294.2 MB
EGAF00008374345 cram 270.5 MB
EGAF00008374346 cram 296.2 MB
EGAF00008374347 cram 256.5 MB
EGAF00008374348 cram 295.2 MB
EGAF00008374349 cram 298.4 MB
EGAF00008374350 cram 224.4 MB
EGAF00008374351 cram 295.5 MB
EGAF00008374352 cram 280.5 MB
EGAF00008374353 cram 274.2 MB
EGAF00008374354 cram 253.7 MB
EGAF00008374355 cram 270.8 MB
EGAF00008374356 cram 433.0 MB
EGAF00008374357 cram 318.0 MB
EGAF00008374358 cram 303.8 MB
EGAF00008374359 cram 302.5 MB
EGAF00008374360 cram 284.9 MB
EGAF00008374361 cram 283.8 MB
EGAF00008374362 cram 320.0 MB
EGAF00008374363 cram 270.6 MB
EGAF00008374364 cram 332.6 MB
EGAF00008374365 cram 342.3 MB
EGAF00008374366 cram 355.1 MB
EGAF00008374367 cram 300.1 MB
EGAF00008374368 cram 373.6 MB
EGAF00008374369 cram 451.9 MB
EGAF00008374370 cram 359.0 MB
EGAF00008374371 cram 380.1 MB
EGAF00008374372 cram 374.9 MB
EGAF00008374373 cram 348.9 MB
EGAF00008374374 cram 334.9 MB
EGAF00008374375 cram 334.1 MB
EGAF00008374376 cram 331.3 MB
EGAF00008374377 cram 350.3 MB
EGAF00008374378 cram 283.8 MB
EGAF00008374379 cram 314.1 MB
EGAF00008374380 cram 379.8 MB
EGAF00008374381 cram 283.9 MB
EGAF00008374382 cram 321.7 MB
EGAF00008374383 cram 345.8 MB
EGAF00008374384 cram 304.7 MB
EGAF00008374385 cram 331.8 MB
EGAF00008374386 cram 307.8 MB
EGAF00008374387 cram 352.0 MB
EGAF00008374388 cram 357.5 MB
EGAF00008374389 cram 334.9 MB
EGAF00008374390 cram 310.0 MB
EGAF00008374391 cram 329.0 MB
EGAF00008374392 cram 372.0 MB
EGAF00008374393 cram 353.0 MB
EGAF00008374394 cram 345.5 MB
EGAF00008374395 cram 402.1 MB
EGAF00008374396 cram 408.9 MB
EGAF00008374397 cram 418.2 MB
EGAF00008374398 cram 365.7 MB
EGAF00008374399 cram 379.0 MB
EGAF00008374400 cram 387.5 MB
EGAF00008374401 cram 412.4 MB
EGAF00008374402 cram 423.6 MB
EGAF00008374403 cram 394.7 MB
EGAF00008374404 cram 341.1 MB
EGAF00008374405 cram 355.5 MB
EGAF00008374406 cram 344.0 MB
EGAF00008374407 cram 395.8 MB
EGAF00008374408 cram 384.9 MB
EGAF00008374409 cram 371.6 MB
EGAF00008374410 cram 366.7 MB
EGAF00008374411 cram 402.7 MB
EGAF00008374412 cram 337.4 MB
EGAF00008374413 cram 343.6 MB
EGAF00008374414 cram 367.3 MB
EGAF00008374415 cram 298.3 MB
EGAF00008374416 cram 323.3 MB
EGAF00008374417 cram 395.4 MB
EGAF00008374418 cram 362.0 MB
EGAF00008374419 cram 369.2 MB
EGAF00008374420 cram 346.4 MB
EGAF00008374421 cram 332.9 MB
EGAF00008374422 cram 396.1 MB
EGAF00008374423 cram 386.0 MB
EGAF00008374424 cram 347.7 MB
EGAF00008374425 cram 416.4 MB
EGAF00008374426 cram 450.0 MB
EGAF00008374427 cram 377.5 MB
EGAF00008374428 cram 349.1 MB
EGAF00008374429 cram 310.0 MB
EGAF00008374430 cram 478.1 MB
EGAF00008374431 cram 394.7 MB
EGAF00008374432 cram 367.6 MB
EGAF00008374433 cram 351.7 MB
EGAF00008374434 cram 410.3 MB
EGAF00008374435 cram 468.6 MB
EGAF00008374436 cram 399.0 MB
EGAF00008374437 cram 371.5 MB
EGAF00008374438 cram 394.2 MB
EGAF00008374439 cram 383.0 MB
EGAF00008374440 cram 291.8 MB
EGAF00008374441 cram 363.8 MB
EGAF00008374442 cram 362.5 MB
EGAF00008374443 cram 335.6 MB
EGAF00008374444 cram 385.2 MB
EGAF00008374445 cram 328.6 MB
EGAF00008374446 cram 305.1 MB
EGAF00008374447 cram 404.7 MB
EGAF00008374448 cram 434.1 MB
EGAF00008374449 cram 403.7 MB
EGAF00008374450 cram 385.8 MB
EGAF00008374451 cram 455.6 MB
EGAF00008374452 cram 413.0 MB
EGAF00008374453 cram 423.8 MB
EGAF00008374454 cram 436.2 MB
EGAF00008374455 cram 432.5 MB
EGAF00008374456 cram 426.7 MB
EGAF00008374457 cram 445.7 MB
EGAF00008374458 cram 427.2 MB
EGAF00008374459 cram 480.2 MB
EGAF00008374460 cram 415.4 MB
EGAF00008374461 cram 482.3 MB
EGAF00008374462 cram 388.0 MB
EGAF00008374463 cram 383.3 MB
EGAF00008374464 cram 366.4 MB
EGAF00008374465 cram 382.5 MB
EGAF00008374466 cram 407.1 MB
EGAF00008374467 cram 427.8 MB
EGAF00008374468 cram 382.7 MB
EGAF00008374469 cram 463.9 MB
EGAF00008374470 cram 432.2 MB
EGAF00008374471 cram 469.0 MB
EGAF00008374472 cram 425.5 MB
EGAF00008374473 cram 435.8 MB
EGAF00008374474 cram 401.9 MB
EGAF00008374475 cram 433.9 MB
EGAF00008374476 cram 384.7 MB
EGAF00008374477 cram 399.0 MB
EGAF00008374478 cram 398.8 MB
EGAF00008374479 cram 478.9 MB
EGAF00008374480 cram 328.4 MB
EGAF00008374481 cram 295.4 MB
EGAF00008374482 cram 290.9 MB
EGAF00008374483 cram 311.5 MB
EGAF00008374484 cram 319.4 MB
EGAF00008374485 cram 309.4 MB
EGAF00008374486 cram 288.8 MB
EGAF00008374487 cram 313.7 MB
EGAF00008374488 cram 372.9 MB
EGAF00008374489 cram 333.8 MB
EGAF00008374490 cram 302.5 MB
EGAF00008374491 cram 287.4 MB
EGAF00008374492 cram 340.0 MB
EGAF00008374493 cram 346.5 MB
EGAF00008374494 cram 352.2 MB
EGAF00008374495 cram 315.4 MB
EGAF00008374496 cram 347.4 MB
EGAF00008374497 cram 311.0 MB
EGAF00008374498 cram 287.3 MB
EGAF00008374499 cram 302.3 MB
EGAF00008374500 cram 329.5 MB
EGAF00008374501 cram 333.9 MB
EGAF00008374502 cram 293.3 MB
EGAF00008374503 cram 315.9 MB
EGAF00008374504 cram 371.6 MB
EGAF00008374505 cram 346.4 MB
EGAF00008374506 cram 322.1 MB
EGAF00008374507 cram 284.2 MB
EGAF00008374508 cram 306.1 MB
EGAF00008374509 cram 317.6 MB
EGAF00008374510 cram 302.9 MB
EGAF00008374511 cram 430.0 MB
EGAF00008374512 cram 348.0 MB
EGAF00008374513 cram 347.2 MB
EGAF00008374514 cram 272.1 MB
EGAF00008374515 cram 346.8 MB
EGAF00008374516 cram 324.0 MB
EGAF00008374517 cram 282.9 MB
EGAF00008374518 cram 397.0 MB
EGAF00008374519 cram 395.6 MB
EGAF00008374520 cram 299.5 MB
EGAF00008374521 cram 328.0 MB
EGAF00008374522 cram 373.4 MB
EGAF00008374523 cram 302.3 MB
EGAF00008374524 cram 368.8 MB
EGAF00008374525 cram 375.1 MB
EGAF00008374526 cram 430.3 MB
EGAF00008374527 cram 445.8 MB
EGAF00008374528 cram 273.6 MB
EGAF00008374529 cram 326.5 MB
EGAF00008374530 cram 382.2 MB
EGAF00008374531 cram 326.1 MB
EGAF00008374532 cram 343.3 MB
EGAF00008374533 cram 288.9 MB
EGAF00008374534 cram 309.3 MB
EGAF00008374535 cram 334.9 MB
EGAF00008374536 cram 322.7 MB
EGAF00008374537 cram 296.0 MB
EGAF00008374538 cram 304.1 MB
EGAF00008374539 cram 331.9 MB
EGAF00008374540 cram 340.2 MB
EGAF00008374541 cram 326.6 MB
EGAF00008374542 cram 385.2 MB
EGAF00008374543 cram 315.6 MB
EGAF00008374544 cram 387.2 MB
EGAF00008374545 cram 347.9 MB
EGAF00008374546 cram 325.4 MB
EGAF00008374547 cram 354.7 MB
EGAF00008374548 cram 375.6 MB
EGAF00008374549 cram 351.8 MB
EGAF00008374550 cram 384.3 MB
EGAF00008374551 cram 367.4 MB
EGAF00008374552 cram 425.2 MB
EGAF00008374553 cram 395.8 MB
EGAF00008374554 cram 388.8 MB
EGAF00008374555 cram 392.7 MB
EGAF00008374556 cram 407.8 MB
EGAF00008374557 cram 401.7 MB
EGAF00008374558 cram 428.3 MB
EGAF00008374559 cram 540.3 MB
EGAF00008374560 cram 393.0 MB
EGAF00008374561 cram 378.1 MB
EGAF00008374562 cram 365.7 MB
EGAF00008374563 cram 403.8 MB
EGAF00008374564 cram 375.3 MB
EGAF00008374565 cram 376.0 MB
EGAF00008374566 cram 349.0 MB
EGAF00008374567 cram 353.8 MB
EGAF00008374568 cram 345.3 MB
EGAF00008374569 cram 339.8 MB
EGAF00008374570 cram 354.5 MB
EGAF00008374571 cram 337.6 MB
EGAF00008374572 cram 316.0 MB
EGAF00008374573 cram 363.5 MB
EGAF00008374574 cram 361.8 MB
EGAF00008374575 cram 313.3 MB
EGAF00008374576 cram 337.0 MB
EGAF00008374577 cram 326.0 MB
EGAF00008374578 cram 347.5 MB
EGAF00008374579 cram 334.1 MB
EGAF00008374580 cram 376.5 MB
EGAF00008374581 cram 444.6 MB
EGAF00008374582 cram 409.8 MB
EGAF00008374583 cram 388.4 MB
EGAF00008374584 cram 442.5 MB
EGAF00008374585 cram 432.5 MB
EGAF00008374586 cram 413.2 MB
EGAF00008374587 cram 400.8 MB
EGAF00008374588 cram 426.8 MB
EGAF00008374589 cram 395.2 MB
EGAF00008374590 cram 387.5 MB
EGAF00008374591 cram 398.0 MB
EGAF00008374592 cram 415.1 MB
EGAF00008374593 cram 423.6 MB
EGAF00008374594 cram 417.9 MB
EGAF00008374595 cram 335.9 MB
462 Files (168.7 GB)