scholarly journals Genome sequencing of normal cells reveals developmental lineages and mutational processes

Nature ◽  
2014 ◽  
Vol 513 (7518) ◽  
pp. 422-425 ◽  
Author(s):  
Sam Behjati ◽  
Meritxell Huch ◽  
Ruben van Boxtel ◽  
Wouter Karthaus ◽  
David C. Wedge ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Normal Cells ◽  
Mutational Processes

scholarly journals Whole-genome sequencing of spermatocytic tumors provides insights into the mutational processes operating in the male germline

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0178169 ◽  
Author(s):  
Eleni Giannoulatou ◽  
Geoffrey J. Maher ◽  
Zhihao Ding ◽  
Ad J. M. Gillis ◽  
Lambert C. J. Dorssers ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Male Germline ◽  
Mutational Processes

The landscape of somatic mutation in normal colorectal epithelial cells

2018 ◽  
Author(s):  
Henry Lee-Six ◽  
Peter Ellis ◽  
Robert J. Osborne ◽  
Mathijs A. Sanders ◽  
Luiza Moore ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Somatic Mutations ◽  
Cell Lineage ◽  
Driver Mutations ◽  
Normal Cells ◽  
Genetic Changes ◽  
Adult Cell ◽  
Neoplastic Change ◽  
Cancer Types ◽  
Mutational Processes

AbstractThe colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions leading to cancer. As for most cancer types, however, understanding of the earliest phases of colorectal neoplastic change, which may occur in morphologically normal tissue, is comparatively limited because of the difficulty of detecting somatic mutations in normal cells. Each colorectal crypt is a small clone of cells derived from a single recently-existing stem cell. Here, we whole genome sequenced hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed, some ubiquitous and continuous, others only found in some individuals, in some crypts or during some phases of the cell lineage from zygote to adult cell. Likely driver mutations were present in ∼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.

scholarly journals The fitness effects of spontaneous mutations nearly unseen by selection in a bacterium with multiple chromosomes

2016 ◽  
Author(s):  
Marcus M. Dillon ◽  
Vaughn S. Cooper
Keyword(s):  
Genome Sequencing ◽  
Common Ancestor ◽  
Burkholderia Cenocepacia ◽  
Missense Mutations ◽  
Spontaneous Mutations ◽  
Nonsense Mutations ◽  
Deletion Mutations ◽  
Fitness Effects ◽  
Quantitative Understanding ◽  
Mutational Processes

ABSTRACTMutation accumulation (MA) experiments employ the strategy of minimizing the population size of evolving lineages to greatly reduce effects of selection on newly arising mutations. Thus, most mutations fix within MA lines independently of their fitness effects. This approach, more recently combined with genome sequencing, has detailed the rates, spectra, and biases of different mutational processes. However, a quantitative understanding of the fitness effects of mutations virtually unseen by selection has remained an untapped opportunity. Here, we analyzed the fitness of 43 sequenced MA lines of the multi-chromosome bacterium Burkholderia cenocepacia that had each undergone 5554 generations of MA and accumulated an average of 6.73 spontaneous mutations. Most lineages exhibited either neutral or deleterious fitness in three different environments in comparison with their common ancestor. The only mutational class that was significantly overrepresented in lineages with reduced fitness was the loss of the plasmid, though nonsense mutations, missense mutations, and coding insertion-deletion mutations were also overrepresented in MA lineages whose fitness had significantly declined. Although the overall distribution of fitness effects was similar between the three environments, the magnitude and even the sign of the fitness of a number of lineages changed with the environment, demonstrating that the fitness of some genotypes was environmentally dependent. These results present an unprecedented picture of the fitness effects of spontaneous mutations in a bacterium with multiple chromosomes and provide greater quantitative support of the theory that the vast majority of spontaneous mutations are neutral or deleterious.

scholarly journals Chromatin accessibility of primary human cancers ties regional mutational processes with tissues of origin

2021 ◽  
Author(s):  
Oliver Ocsenas ◽  
Jüri Reimand
Keyword(s):  
Human Cancer ◽  
Replication Timing ◽  
Chromatin Accessibility ◽  
Cancer Genes ◽  
Cancer Evolution ◽  
Normal Cells ◽  
Cancer Genomes ◽  
Localized Mutagenesis ◽  
Passenger Mutations ◽  
Mutational Processes

Regional mutagenesis in cancer genomes associates with DNA replication timing (RT) and chromatin accessibility (CA) of normal cells, however human cancer epigenomes remain uncharacterized in this context. Here we model megabase-scale mutation frequencies in 2517 cancer genomes with 773 CA and RT profiles of cancers and normal cells. We find that CA profiles of matching cancers, rather than normal cells, predict regional mutagenesis and mutational signatures, indicating that most passenger mutations follow the epigenetic landscapes of transformed cells. Carcinogen-induced and unannotated signatures show the strongest associations with epigenomes. Associations with normal cells in melanomas, lymphomas and SBS1 signatures suggest earlier occurrence of mutations in cancer evolution. Frequently mutated regions unexplained by CA and RT are enriched in cancer genes and developmental pathways, reflecting contributions of localized mutagenesis and positive selection. These results underline the complex interplay of mutational processes, genome function and evolution in cancer and tissues of origin.

Immunoenzymatic demonstration of the simultaneous presence of transferrin, hemopexin and albumin in a same hepatocyte and their ultrastructural localization

1978 ◽  
Vol 36 (2) ◽  
pp. 88-89
Author(s):  
M. Kraemer ◽  
J. Foucrier ◽  
J. Vassy ◽  
M.T. Chalumeau
Keyword(s):  
Plasma Proteins ◽  
Rat Hepatocytes ◽  
Ultrastructural Localization ◽  
Carrier Proteins ◽  
Normal Cells ◽  
Adult Rat ◽  
Adult Rat Hepatocytes ◽  
Monospecific Antisera ◽  
Different Levels

Some authors using immunofluorescent techniques had already suggested that some hepatocytes are able to synthetize several plasma proteins. In vitro studies on normal cells or on cells issued of murine hepatomas raise the same conclusion. These works could be indications of an hepatocyte functionnal non-specialization, meanwhile the authors never give direct topographic proofs suitable with this hypothesis.The use of immunoenzymatic techniques after obtention of monospecific antisera had seemed to us useful to bring forward a better knowledge of this problem. We have studied three carrier proteins (transferrin = Tf, hemopexin = Hx, albumin = Alb) operating at different levels in iron metabolism by demonstrating and localizing the adult rat hepatocytes involved in their synthesis.Immunological, histological and ultrastructural methods have been described in a previous work.

Localization of Gallium-67 in Peritoneal Cells by Electron Microscopic Autoradiography

1973 ◽  
Vol 31 ◽  
pp. 404-405
Author(s):  
D. C. Swartzendruber ◽  
Norma L. Idoyaga-Vargas
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Tumor Tissue ◽  
Soft Tissue Tumors ◽  
Clinical Usefulness ◽  
Electron Microscopic ◽  
Normal Cells ◽  
Electron Microscopic Autoradiography ◽  
Peritoneal Cells ◽  
Gallium 67

The radionuclide gallium-67 (67Ga) localizes preferentially but not specifically in many human and experimental soft-tissue tumors. Because of this localization, 67Ga is used in clinical trials to detect humar. cancers by external scintiscanning methods. However, the fact that 67Ga does not localize specifically in tumors requires for its eventual clinical usefulness a fuller understanding of the mechanisms that control its deposition in both malignant and normal cells. We have previously reported that 67Ga localizes in lysosomal-like bodies, notably, although not exclusively, in macrophages of the spocytaneous AKR thymoma. Further studies on the uptake of 67Ga by macrophages are needed to determine whether there are factors related to malignancy that might alter the localization of 67Ga in these cells and thus provide clues to discovering the mechanism of 67Ga localization in tumor tissue.

Quantitative Freeze Fracture Studies of Gap Junctions in Somatic Cell Hybrids, Their Parents, and Revertants

1976 ◽  
Vol 34 ◽  
pp. 218-219
Author(s):  
W. J. Larsen ◽  
R. Azarnia ◽  
W. R. Loewenstein
Keyword(s):  
Gap Junctions ◽  
Striated Muscle ◽  
Freeze Fracture ◽  
Cell Movement ◽  
Dye Molecules ◽  
Somatic Cell Hybrids ◽  
Cell Coupling ◽  
Normal Cells ◽  
Mediate Cell ◽  
Almost All

Although the physiological significance of the gap junction remains unspecified, these membrane specializations are now recognized as common to almost all normal cells (excluding adult striated muscle and some nerve cells) and are found in organisms ranging from the coelenterates to man. Since it appears likely that these structures mediate the cell-to-cell movement of ions and small dye molecules in some electrical tissues, we undertook this study with the objective of determining whether gap junctions in inexcitable tissues also mediate cell-to-cell coupling.To test this hypothesis, a coupling, human Lesh-Nyhan (LN) cell was fused with a non-coupling, mouse cl-1D cell, and the hybrids, revertants, and parental cells were analysed for coupling with respect both to ions and fluorescein and for membrane junctions with the freeze fracture technique.

Genome Sequencing Set to Hunt for Alzheimer's Clues

2012 ◽  
Vol 45 (13) ◽  
pp. 36
Author(s):  
MICHELE G. SULLIVAN
Keyword(s):  
Genome Sequencing
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