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Targeted sequencing of Human esophageal epithelium microbiopsies

NOTCH1 mutant clones occupy the majority of normal human esophagus by middle age, but are comparatively rare in esophageal cancers, suggesting NOTCH1 mutations may promote clonal expansion but impede carcinogenesis. Here we test this hypothesis. Visualizing and sequencing NOTCH1 mutant clones in aging normal human esophagus, reveals frequent biallelic mutations that block NOTCH1 signaling.  In mouse esophagus, heterozygous Notch1 mutation confers a competitive advantage over wild type cells, an effect enhanced by loss of the second allele.  Notch1 loss alters transcription but has minimal effects on epithelial structure and cell dynamics. In a carcinogenesis model, Notch1 mutations were less prevalent in tumors than normal epithelium. Deletion of Notch1 reduced tumor growth, an effect recapitulated by anti-NOTCH1 antibody treatment.  We conclude that Notch1 mutations in normal epithelium are beneficial as wild type Notch1 promotes tumor expansion. NOTCH1 blockade has therapeutic potential in esophageal squamous tumors.

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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

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
EGAF00005001836 cram 194.3 MB
EGAF00005001837 cram 180.6 MB
EGAF00005001838 cram 191.1 MB
EGAF00005001839 cram 161.9 MB
EGAF00005001840 cram 237.5 MB
EGAF00005001841 cram 249.2 MB
EGAF00005001842 cram 205.4 MB
EGAF00005001843 cram 191.8 MB
EGAF00005001844 cram 210.8 MB
EGAF00005001845 cram 243.7 MB
EGAF00005001846 cram 273.0 MB
EGAF00005001847 cram 268.3 MB
EGAF00005001848 cram 241.3 MB
EGAF00005001849 cram 197.8 MB
EGAF00005001850 cram 194.1 MB
EGAF00005001851 cram 218.4 MB
EGAF00005001852 cram 106.2 MB
EGAF00005001853 cram 237.2 MB
EGAF00005001854 cram 185.1 MB
EGAF00005001855 cram 249.3 MB
EGAF00005001856 cram 170.9 MB
EGAF00005001857 cram 201.0 MB
EGAF00005001858 cram 209.1 MB
EGAF00005001859 cram 258.6 MB
EGAF00005001860 cram 112.1 MB
EGAF00005001861 cram 180.4 MB
EGAF00005001862 cram 241.2 MB
EGAF00005001863 cram 210.1 MB
EGAF00005001864 cram 206.6 MB
EGAF00005001865 cram 226.8 MB
EGAF00005001866 cram 196.0 MB
EGAF00005001867 cram 182.0 MB
EGAF00005001868 cram 177.5 MB
EGAF00005001869 cram 633.9 MB
EGAF00005001870 cram 204.4 MB
EGAF00005001871 cram 321.0 MB
EGAF00005001872 cram 383.9 MB
EGAF00005001873 cram 158.6 MB
EGAF00005001874 cram 224.6 MB
EGAF00005001875 cram 153.8 MB
EGAF00005001876 cram 312.1 MB
EGAF00005001877 cram 319.7 MB
EGAF00005001878 cram 237.4 MB
EGAF00005001879 cram 296.0 MB
EGAF00005001880 cram 406.0 MB
EGAF00005001881 cram 206.4 MB
EGAF00005001882 cram 263.4 MB
EGAF00005001883 cram 229.3 MB
EGAF00005001884 cram 244.7 MB
EGAF00005001885 cram 206.8 MB
EGAF00005001886 cram 243.9 MB
EGAF00005001887 cram 274.4 MB
EGAF00005001888 cram 246.4 MB
EGAF00005001889 cram 179.7 MB
EGAF00005001890 cram 257.4 MB
EGAF00005001891 cram 157.0 MB
EGAF00005001892 cram 219.7 MB
EGAF00005001893 cram 193.8 MB
EGAF00005001894 cram 222.6 MB
EGAF00005001895 cram 253.4 MB
EGAF00005001896 cram 303.0 MB
EGAF00005001897 cram 337.0 MB
EGAF00005001898 cram 283.8 MB
EGAF00006166367 cram 819.1 MB
EGAF00006166368 cram 663.3 MB
EGAF00006166369 cram 567.3 MB
EGAF00006166370 cram 662.3 MB
EGAF00006166371 cram 595.3 MB
EGAF00006166372 cram 745.3 MB
EGAF00006166373 cram 606.9 MB
EGAF00006166374 cram 725.9 MB
EGAF00006166375 cram 663.3 MB
EGAF00006166376 cram 725.8 MB
EGAF00006166377 cram 545.5 MB
EGAF00006166378 cram 749.4 MB
EGAF00006166379 cram 726.0 MB
EGAF00006166380 cram 720.0 MB
EGAF00006166381 cram 513.9 MB
EGAF00006166382 cram 689.8 MB
EGAF00006166383 cram 515.7 MB
EGAF00006166384 cram 736.1 MB
EGAF00006166385 cram 320.8 MB
EGAF00006166386 cram 732.0 MB
EGAF00006166387 cram 604.6 MB
EGAF00006166388 cram 649.1 MB
EGAF00006166389 cram 674.4 MB
EGAF00006166390 cram 581.1 MB
EGAF00006166391 cram 690.5 MB
EGAF00006166392 cram 785.5 MB
EGAF00006166393 cram 561.2 MB
EGAF00006166394 cram 795.6 MB
EGAF00006166395 cram 721.2 MB
92 Files (33.9 GB)