The landscape of somatic mutation in normal colorectal epithelial cells

The colorectal adenoma–carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer 1 . However, our understanding of the earliest phases of colorectal neoplastic changes—which may occur in morp...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Nature (London) Ročník 574; číslo 7779; s. 532 - 537
Hlavní autoři:	Lee-Six, Henry, Olafsson, Sigurgeir, Ellis, Peter, Osborne, Robert J., Sanders, Mathijs A., Moore, Luiza, Georgakopoulos, Nikitas, Torrente, Franco, Noorani, Ayesha, Goddard, Martin, Robinson, Philip, Coorens, Tim H. H., O’Neill, Laura, Alder, Christopher, Wang, Jingwei, Fitzgerald, Rebecca C., Zilbauer, Matthias, Coleman, Nicholas, Saeb-Parsy, Kourosh, Martincorena, Inigo, Campbell, Peter J., Stratton, Michael R.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.10.2019 Nature Publishing Group
Témata:	45/100 45/22 45/23 45/41 631/532/2437 631/67/1504/1885/1393 631/67/69 Adenoma - genetics Adenoma - pathology Aged Axin Protein - genetics Carcinoma - genetics Carcinoma - pathology Cell Transformation, Neoplastic Clone Cells - cytology Clone Cells - metabolism Colon (Anatomy) Colon - cytology Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology DNA Copy Number Variations DNA Mutational Analysis Epithelial cells Epithelial Cells - cytology Epithelial Cells - metabolism Female Genetic aspects Humanities and Social Sciences Humans Intestinal Mucosa - cytology Intestinal Mucosa - metabolism Intestinal Mucosa - pathology Male Middle Aged multidisciplinary Mutation Mutation (Biology) Physiological aspects Prodromal Symptoms Rectum Rectum - cytology Science Science (multidisciplinary) Stem Cells - cytology Stem Cells - metabolism United Kingdom
ISSN:	0028-0836, 1476-4687, 1476-4687
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	The colorectal adenoma–carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer 1 . However, our understanding of the earliest phases of colorectal neoplastic changes—which may occur in morphologically normal tissue—is comparatively limited, as for most cancer types. Here we use whole-genome sequencing to analyse hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed; some of these were ubiquitous and continuous, whereas others were only found in some individuals, in some crypts or during certain periods of life. Probable driver mutations were present in around 1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium. Colorectal cancers exhibit substantially increased mutational burdens relative to normal cells. Sequencing normal colorectal cells provides quantitative insights into the genomic and clonal evolution of cancer. Genome sequencing of hundreds of normal colonic crypts from 42 individuals sheds light on mutational processes and driver mutations in normal colorectal epithelial cells.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-019-1672-7