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DOI | 10.1126/science.aau3879 |
Somatic mutant clones colonize the human esophagus with age | |
Martincorena, Inigo1; Fowler, Joanna C.1; Wabik, Agnieszka1; Lawson, Andrew R. J.1; Abascal, Federico1; Hall, Michael W. J.1,2; Cagan, Alex1; Murai, Kasumi1; Mahbubani, Krishnaa3,4; Stratton, Michael R.1; Fitzgerald, Rebecca C.2; Handford, Penny A.5; Campbell, Peter J.1,6; Saeb-Parsy, Kourosh3,4; Jones, Philip H.1 | |
2018-11-23 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6417页码:911-+ |
文章类型 | Article |
语种 | 英语 |
国家 | England |
英文摘要 | The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53 mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000451124500034 |
WOS关键词 | SQUAMOUS-CELL CARCINOMA ; MUTATIONAL PROCESSES ; BARRETTS-ESOPHAGUS ; CANCER-RISK ; NOTCH1 ; DIFFERENTIATION ; HEMATOPOIESIS ; EXPRESSION ; SIGNATURES ; LANDSCAPE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200133 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Wellcome Sanger Inst, Hinxton CB10 1SA, Cambs, England; 2.Univ Cambridge, Hutchison MRC Res Ctr, MRC Canc Unit, Cambridge CB2 0XZ, England; 3.Univ Cambridge, Dept Surg, Biomed Campus, Cambridge CB2 2QQ, England; 4.Univ Cambridge, Cambridge NIHR Biomed Res Ctr, Biomed Campus, Cambridge CB2 2QQ, England; 5.Univ Oxford, Dept Biochem, South Parks Rd, Oxford OX1 3QU, England; 6.Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England |
推荐引用方式 GB/T 7714 | Martincorena, Inigo,Fowler, Joanna C.,Wabik, Agnieszka,et al. Somatic mutant clones colonize the human esophagus with age[J]. SCIENCE,2018,362(6417):911-+. |
APA | Martincorena, Inigo.,Fowler, Joanna C..,Wabik, Agnieszka.,Lawson, Andrew R. J..,Abascal, Federico.,...&Jones, Philip H..(2018).Somatic mutant clones colonize the human esophagus with age.SCIENCE,362(6417),911-+. |
MLA | Martincorena, Inigo,et al."Somatic mutant clones colonize the human esophagus with age".SCIENCE 362.6417(2018):911-+. |
条目包含的文件 | 条目无相关文件。 |
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