EGAGenomicsIllumina HiSeq 2000Cancer Genomicshttps://ega-archive.org/studies/EGAS00001000860EGAEGA study EGAS00001000860Use of deep sequencing to detect clonal mutations in sun exposed human epidermis - whole genomeEGArestrictedHow somatic mutations accumulate in normal cells is central to understanding cancer development but is poorly understood. We performed ultradeep sequencing of 74 cancer genes in small (0.8 to 4.7 square millimeters) biopsies of normal skin. Across 234 biopsies of sun-exposed eyelid epidermis from four individuals, the burden of somatic mutations averaged two to six mutations per megabase per cell, similar to that seen in many cancers, and exhibited characteristic signatures of exposure to ultraviolet light. Remarkably, multiple cancer genes are under strong positive selection even in physiologically normal skin, including most of the key drivers of cutaneous squamous cell carcinomas. Positively selected mutations were found in 18 to 32% of normal skin cells at a density of ~140 driver mutations per square centimeter. We observed variability in the driver landscape among individuals and variability in the sizes of clonal expansions across genes. Thus, aged sun-exposed skin is a patchwork of thousands of evolving clones with over a quarter of cells carrying cancer-causing mutations while maintaining the physiological functions of epidermis.Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin.Martincorena Iñigo I, Roshan Amit A, Gerstung Moritz M, Ellis Peter P, Van Loo Peter P, McLaren Stuart S, Wedge David C DC, Fullam Anthony A, Alexandrov Ludmil B LB, Tubio Jose M JM, Stebbings Lucy L, Menzies Andrew A, Widaa Sara S, Stratton Michael R MR, Jones Philip H PH, Campbell Peter J PJHuman, Mutations, extruding from, vertebrate epidermis, human being, Man (Taxonomy), skin, Homo sapiens, Modern Man, exits through, Modern, epidermis (sensu Metazoa), whole genome., outer epidermal layer, outer epithelial layer, exposed, hypodermis, hypoderm, Man, human, epidermisdermis plus epidermis plus hypodermis, the integument, region of skin, human being, Oct-11a, Malignant Neoplasm, pelt, Otf-11, Skn-li, selection process, Neoplasms, Modern, Benign Neoplasm, skin zone, integumental organ, Tumor, Malignant, epidermis, Human, Mutations, skin plus hypodermis, Benign, Oct11, skin region, Homo sapiens, BC033609, Neoplasm, Skin-1a, tegument, Skin, Man, integumentum commune, skin benign neoplasm, average, Man (Taxonomy), skin, Malignancy, vertebrate integument, dermoid system, entire skin, Benign Neoplasms, Cancers, Skn-1a., SKIN, human, mKIAA0493, Malignant Neoplasms, Epoc-1, Neoplasias, skin organ, portion of skin, vertebrate epidermis, integument, Modern Man, Fam91a1, Otf11, Malignancies, entire integument, other neoplasm, AV220772, dermal system, skin and subcutaneous tissue, Neoplasia, Cancer, Tumorsdermis plus epidermis plus hypodermis, the integument, region of skin, Oct-11a, human being, pelt, Tissue., Otf-11, Skn-li, adult stage, Modern, skin zone, integumental organ, epidermis, Human, Mutations, skin plus hypodermis, Oct11, skin region, Homo sapiens, BC033609, Skin-1a, tegument, Skin, Adults, Man, adult, integumentum commune, Skn-1a, skin benign neoplasm, study, skin, Man (Taxonomy), Biopsies, vertebrate integument, dermoid system, entire skin, SKIN, human, mKIAA0493, Epoc-1, skin organ, portion of skin, vertebrate epidermis, integument, Modern Man, Fam91a1, Otf11, entire integument, AV220772, dermal system, skin and subcutaneous tissuedermis plus epidermis plus hypodermis, the integument, d230, region of skin, Materials, single-organism developmental process, pelt, Otf-11, Skn-li, selection process, Neoplasms, square centimetre, postnatal development, Benign Neoplasm, Gene, dTAFII250, growth and development, Visible Light, Tumor, Squamous Cell Carcinoma, Malignant, EfW1, epidermis, Ly113, Planocellular Carcinomas, Mutations, qr, dmTAF[[II]]230, Readability, Epidermoid Carcinomas, reduced, resilient, dmTAF1, Taf230, tough, Carrying, tiny, integumentum commune, Skn-1a, TAF250, average, Eyelid, strong, Taf200, dTAF[[II]]250, Genetic, skin, Biopsies, TFIID TAF250, cm^[2], Malignancy, cel, cell, hypoplasia, dermoid system, entire skin, Taf1p, outer epithelial layer, Visible, SKIN, Neoplasias, dTAF250, skin organ, TNFSF14, extruding from, malignant neoplasm, epidermis., Fam91a1, Otf11, Malignancies, epidermis (sensu Metazoa), TR2, TAF, AV220772, skin and subcutaneous tissue, palpebrae, Cancer, Tumors, small, Carcinoma, dTAF[[II]]230, TAF[[II]]250, Oct-11a, Radiation, Malignant Neoplasm, UNQ391/PRO726, exits through, TAF200, skin zone, l(3)84Ab, Planocellular, Light, integumental organ, BG:DS00004.13, Squamous, hypodermis, TAFII-250, TAF250/230, Cistrons, CD258, Cell, dTAF230, development, skin plus hypodermis, TAFII250, MT, Benign, Oct11, skin region, LIGHT, p230, BC033609, qtr, Neoplasm, TAF[[II]]250/230, Genetic Materials, TFIID, Squamous Cell Carcinomas, Skin-1a, tegument, Skin, Genetic Material, skin benign neoplasm, Visible Radiations, Radiations, Carcinomas, Taf[[II]]250, Squamous Carcinoma, primary cancer, Visible Radiation, Squamous Cell, Planocellular Carcinoma, TAF[[II]]230, HVEML, Epidermoid, underdeveloped, HVEM-L, postnatal growth, Photoradiation, vertebrate integument, Benign Neoplasms, blephara, TAF[II]250, Cancers, Understanding, exposed, CG17603, TAF[[II]], malignant tumor, mKIAA0493, LTg, Malignant Neoplasms, Epoc-1, portion of skin, vertebrate epidermis, DmelCG17603, Photoradiations, integument, Taf250, Material, SR3-5, Squamous Carcinomas, Cistron, entire integument, outer epidermal layer, Epidermoid Carcinoma, growth, dermal system, hypoderm, Neoplasia, TAF230, Elderly, TAF1falseUse of deep sequencing to detect clonal mutations in sun exposed human epidermis whole genomeDeep sequencing of two skin biopsies to study the landscape of somatic mutations in human adult tissues.2017-07-26 15:39:25EGAS00001000860960625999502EGAD00001001123EGAC00001000000