LIVIVO - Search results -

Search results

Result 1 - 10 of total 31

Search options

Article: The SPECTRUM Consortium: a new UK Prevention Research Partnership consortium focussed on the commercial determinants of health, the prevention of non-communicable diseases, and the reduction of health inequalities.

Horton, Marie / Perman-Howe, Parvati R / Angus, Colin / Bishop, Julie / Bogdanovica, Ilze / Brennan, Alan / Britton, John / Brose, Leonie S / Brown, Jamie / Collin, Jeff / Dockrell, Martin / Fitzgerald, Niamh / Friel, Sharon / Gillespie, Duncan / Gilmore, Anna B / Hill, Sarah E / Knai, Cecile / Langley, Tessa / Martin, Sancha /

McNeill, Ann / Moore, Graham / Munafò, Marcus R / Murray, Rachael L / Opazo Breton, Magdelena / Pearce, Jamie / Petticrew, Mark / Reid, Garth / Robson, Deborah / Rutter, Harry / Shahab, Lion / Shortt, Niamh / Smith, Katherine / Syrett, Keith / Bauld, Linda

Wellcome open research

2021 Volume 6, Page(s) 6

Abstract: The main causes of non-communicable diseases (NCDs), health inequalities and health inequity include consumption of unhealthy commodities such as tobacco, alcohol and/or foods high in fat, salt and/or sugar. These exposures are preventable, but the ... ...

Abstract	The main causes of non-communicable diseases (NCDs), health inequalities and health inequity include consumption of unhealthy commodities such as tobacco, alcohol and/or foods high in fat, salt and/or sugar. These exposures are preventable, but the commodities involved are highly profitable. The economic interests of 'Unhealthy Commodity Producers' (UCPs) often conflict with health goals but their role in determining health has received insufficient attention. In order to address this gap, a new research consortium has been established. This open letter introduces the SPECTRUM (
Language	English
Publishing date	2021-01-14
Publishing country	England
Document type	Journal Article
ISSN	2398-502X
ISSN	2398-502X
DOI	10.12688/wellcomeopenres.16318.1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The Driver Mutational Landscape of Ovarian Squamous Cell Carcinomas Arising in Mature Cystic Teratoma.

Cooke, Susanna L / Ennis, Darren / Evers, Lisa / Dowson, Suzanne / Chan, Mei Yen / Paul, James / Hirschowitz, Lynn / Glasspool, Rosalind M / Singh, Naveena / Bell, Sarah / Day, Elizabeth / Kochman, Agata / Wilkinson, Nafisa / Beer, Philip / Martin, Sancha / Millan, David / Biankin, Andrew V / McNeish, Iain A

Clinical cancer research : an official journal of the American Association for Cancer Research

2017 Volume 23, Issue 24, Page(s) 7633–7640

Abstract: Purpose: ...

Abstract	Purpose:
MeSH term(s)	Adult ; Aged ; Carcinoma, Ovarian Epithelial ; Carcinoma, Squamous Cell/genetics ; Cell Transformation, Neoplastic ; Class I Phosphatidylinositol 3-Kinases/genetics ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/genetics ; DNA Copy Number Variations/genetics ; Female ; Humans ; Middle Aged ; Mutation ; Neoplasm Proteins/genetics ; Neoplasms, Glandular and Epithelial/genetics ; Neoplasms, Glandular and Epithelial/pathology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Teratoma/genetics ; Teratoma/pathology ; Tumor Suppressor Protein p53/genetics
Chemical Substances	CDKN2A protein, human ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18 ; Neoplasm Proteins ; TP53 protein, human ; Tumor Suppressor Protein p53 ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3CA protein, human (EC 2.7.1.137)
Language	English
Publishing date	2017-09-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-17-1789
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4223: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Partially methylated domains are hypervariable in breast cancer and fuel widespread CpG island hypermethylation.

Brinkman, Arie B / Nik-Zainal, Serena / Simmer, Femke / Rodríguez-González, F Germán / Smid, Marcel / Alexandrov, Ludmil B / Butler, Adam / Martin, Sancha / Davies, Helen / Glodzik, Dominik / Zou, Xueqing / Ramakrishna, Manasa / Staaf, Johan / Ringnér, Markus / Sieuwerts, Anieta / Ferrari, Anthony / Morganella, Sandro / Fleischer, Thomas / Kristensen, Vessela /

Gut, Marta / van de Vijver, Marc J / Børresen-Dale, Anne-Lise / Richardson, Andrea L / Thomas, Gilles / Gut, Ivo G / Martens, John W M / Foekens, John A / Stratton, Michael R / Stunnenberg, Hendrik G

Nature communications

2019 Volume 10, Issue 1, Page(s) 1749

Abstract: Global loss of DNA methylation and CpG island (CGI) hypermethylation are key epigenomic aberrations in cancer. Global loss manifests itself in partially methylated domains (PMDs) which extend up to megabases. However, the distribution of PMDs within and ... ...

Abstract	Global loss of DNA methylation and CpG island (CGI) hypermethylation are key epigenomic aberrations in cancer. Global loss manifests itself in partially methylated domains (PMDs) which extend up to megabases. However, the distribution of PMDs within and between tumor types, and their effects on key functional genomic elements including CGIs are poorly defined. We comprehensively show that loss of methylation in PMDs occurs in a large fraction of the genome and represents the prime source of DNA methylation variation. PMDs are hypervariable in methylation level, size and distribution, and display elevated mutation rates. They impose intermediate DNA methylation levels incognizant of functional genomic elements including CGIs, underpinning a CGI methylator phenotype (CIMP). Repression effects on tumor suppressor genes are negligible as they are generally excluded from PMDs. The genomic distribution of PMDs reports tissue-of-origin and may represent tissue-specific silent regions which tolerate instability at the epigenetic, transcriptomic and genetic level.
MeSH term(s)	Breast Neoplasms/genetics ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Female ; Humans ; Logistic Models
Language	English
Publishing date	2019-04-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-09828-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.

Nik-Zainal, Serena / Wedge, David C / Alexandrov, Ludmil B / Petljak, Mia / Butler, Adam P / Bolli, Niccolo / Davies, Helen R / Knappskog, Stian / Martin, Sancha / Papaemmanuil, Elli / Ramakrishna, Manasa / Shlien, Adam / Simonic, Ingrid / Xue, Yali / Tyler-Smith, Chris / Campbell, Peter J / Stratton, Michael R

Nature genetics

2014 Volume 46, Issue 5, Page(s) 487–491

Abstract: The somatic mutations in a cancer genome are the aggregate outcome of one or more mutational processes operative through the lifetime of the individual with cancer. Each mutational process leaves a characteristic mutational signature determined by the ... ...

Abstract	The somatic mutations in a cancer genome are the aggregate outcome of one or more mutational processes operative through the lifetime of the individual with cancer. Each mutational process leaves a characteristic mutational signature determined by the mechanisms of DNA damage and repair that constitute it. A role was recently proposed for the APOBEC family of cytidine deaminases in generating particular genome-wide mutational signatures and a signature of localized hypermutation called kataegis. A germline copy number polymorphism involving APOBEC3A and APOBEC3B, which effectively deletes APOBEC3B, has been associated with modestly increased risk of breast cancer. Here we show that breast cancers in carriers of the deletion show more mutations of the putative APOBEC-dependent genome-wide signatures than cancers in non-carriers. The results suggest that the APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through increased activity of APOBEC-dependent mutational processes, although the mechanism by which this increase in activity occurs remains unknown.
MeSH term(s)	Breast Neoplasms/genetics ; Cytidine Deaminase/genetics ; DNA Copy Number Variations/genetics ; Female ; Genetic Markers/genetics ; Genetic Predisposition to Disease/genetics ; Humans ; Minor Histocompatibility Antigens ; Mutagenesis ; Proteins/genetics ; Sequence Deletion/genetics
Chemical Substances	Genetic Markers ; Minor Histocompatibility Antigens ; Proteins ; APOBEC3A protein, human (EC 3.5.4.5) ; APOBEC3B protein, human (EC 3.5.4.5) ; Cytidine Deaminase (EC 3.5.4.5)
Language	English
Publishing date	2014-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/ng.2955
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 46: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma.

Behjati, Sam / Tarpey, Patrick S / Haase, Kerstin / Ye, Hongtao / Young, Matthew D / Alexandrov, Ludmil B / Farndon, Sarah J / Collord, Grace / Wedge, David C / Martincorena, Inigo / Cooke, Susanna L / Davies, Helen / Mifsud, William / Lidgren, Mathias / Martin, Sancha / Latimer, Calli / Maddison, Mark / Butler, Adam P / Teague, Jon W /

Pillay, Nischalan / Shlien, Adam / McDermott, Ultan / Futreal, P Andrew / Baumhoer, Daniel / Zaikova, Olga / Bjerkehagen, Bodil / Myklebost, Ola / Amary, M Fernanda / Tirabosco, Roberto / Van Loo, Peter / Stratton, Michael R / Flanagan, Adrienne M / Campbell, Peter J

Nature communications

2017 Volume 8, Page(s) 15936

Abstract: Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding ... ...

Abstract	Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike.
MeSH term(s)	Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Insulin-Like Growth Factor I/genetics ; Insulin-Like Growth Factor I/metabolism ; Male ; Middle Aged ; Mutation ; Osteosarcoma/genetics ; Osteosarcoma/metabolism ; Receptor, IGF Type 1/genetics ; Receptor, IGF Type 1/metabolism ; Signal Transduction ; Young Adult
Chemical Substances	IGF1 protein, human ; Insulin-Like Growth Factor I (67763-96-6) ; Receptor, IGF Type 1 (EC 2.7.10.1)
Language	English
Publishing date	2017-06-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/ncomms15936
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures.

Davies, Helen / Glodzik, Dominik / Morganella, Sandro / Yates, Lucy R / Staaf, Johan / Zou, Xueqing / Ramakrishna, Manasa / Martin, Sancha / Boyault, Sandrine / Sieuwerts, Anieta M / Simpson, Peter T / King, Tari A / Raine, Keiran / Eyfjord, Jorunn E / Kong, Gu / Borg, Åke / Birney, Ewan / Stunnenberg, Hendrik G / van de Vijver, Marc J /

Børresen-Dale, Anne-Lise / Martens, John W M / Span, Paul N / Lakhani, Sunil R / Vincent-Salomon, Anne / Sotiriou, Christos / Tutt, Andrew / Thompson, Alastair M / Van Laere, Steven / Richardson, Andrea L / Viari, Alain / Campbell, Peter J / Stratton, Michael R / Nik-Zainal, Serena

Nature medicine

2017 Volume 23, Issue 4, Page(s) 517–525

Abstract: Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 ( ... ...

Abstract	Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.
MeSH term(s)	Area Under Curve ; BRCA1 Protein/deficiency ; BRCA1 Protein/genetics ; BRCA2 Protein/deficiency ; BRCA2 Protein/genetics ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms, Male/genetics ; DNA Mutational Analysis ; Female ; Humans ; Logistic Models ; Male ; Models, Genetic ; Mutation ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human ; Poly(ADP-ribose) Polymerase Inhibitors
Language	English
Publishing date	2017-03-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm.4292
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 39: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The circular RNome of primary breast cancer.

Smid, Marcel / Wilting, Saskia M / Uhr, Katharina / Rodríguez-González, F Germán / de Weerd, Vanja / Prager-Van der Smissen, Wendy J C / van der Vlugt-Daane, Michelle / van Galen, Anne / Nik-Zainal, Serena / Butler, Adam / Martin, Sancha / Davies, Helen R / Staaf, Johan / van de Vijver, Marc J / Richardson, Andrea L / MacGrogan, Gaëten / Salgado, Roberto / van den Eynden, Gert G G M / Purdie, Colin A /

Genome research

2019 Volume 29, Issue 3, Page(s) 356–366

Abstract: Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped ...

Abstract	Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently. Of the circRNAs that match exon boundaries of the same gene, 668 showed a poor or even negative (
MeSH term(s)	Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; CREB-Binding Protein/genetics ; CREB-Binding Protein/metabolism ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Female ; Humans ; Lymphatic Metastasis ; MCF-7 Cells ; RNA/genetics ; RNA/metabolism ; RNA, Circular ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Transcriptome
Chemical Substances	Biomarkers, Tumor ; CNOT2 protein, human ; Carrier Proteins ; RERE protein, human ; RNA, Circular ; Repressor Proteins ; RNA (63231-63-0) ; CREB-Binding Protein (EC 2.3.1.48) ; CREBBP protein, human (EC 2.3.1.48)
Language	English
Publishing date	2019-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.238121.118
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3729: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 8: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The topography of mutational processes in breast cancer genomes.

Morganella, Sandro / Alexandrov, Ludmil B / Glodzik, Dominik / Zou, Xueqing / Davies, Helen / Staaf, Johan / Sieuwerts, Anieta M / Brinkman, Arie B / Martin, Sancha / Ramakrishna, Manasa / Butler, Adam / Kim, Hyung-Yong / Borg, Åke / Sotiriou, Christos / Futreal, P Andrew / Campbell, Peter J / Span, Paul N / Van Laere, Steven / Lakhani, Sunil R /

Eyfjord, Jorunn E / Thompson, Alastair M / Stunnenberg, Hendrik G / van de Vijver, Marc J / Martens, John W M / Børresen-Dale, Anne-Lise / Richardson, Andrea L / Kong, Gu / Thomas, Gilles / Sale, Julian / Rada, Cristina / Stratton, Michael R / Birney, Ewan / Nik-Zainal, Serena

Nature communications

2016 Volume 7, Page(s) 11383

Abstract: Somatic mutations in human cancers show unevenness in genomic distribution that correlate with aspects of genome structure and function. These mutations are, however, generated by multiple mutational processes operating through the cellular lineage ... ...

Abstract	Somatic mutations in human cancers show unevenness in genomic distribution that correlate with aspects of genome structure and function. These mutations are, however, generated by multiple mutational processes operating through the cellular lineage between the fertilized egg and the cancer cell, each composed of specific DNA damage and repair components and leaving its own characteristic mutational signature on the genome. Using somatic mutation catalogues from 560 breast cancer whole-genome sequences, here we show that each of 12 base substitution, 2 insertion/deletion (indel) and 6 rearrangement mutational signatures present in breast tissue, exhibit distinct relationships with genomic features relating to transcription, DNA replication and chromatin organization. This signature-based approach permits visualization of the genomic distribution of mutational processes associated with APOBEC enzymes, mismatch repair deficiency and homologous recombinational repair deficiency, as well as mutational processes of unknown aetiology. Furthermore, it highlights mechanistic insights including a putative replication-dependent mechanism of APOBEC-related mutagenesis.
MeSH term(s)	Apolipoproteins B/genetics ; Apolipoproteins B/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Chromatin/chemistry ; Chromatin/metabolism ; DNA Damage ; DNA Repair ; DNA Replication ; Female ; Genome, Human ; Humans ; MCF-7 Cells ; Mutagenesis ; Mutation ; Sequence Analysis, DNA ; Transcription, Genetic
Chemical Substances	Apolipoproteins B ; Chromatin
Language	English
Publishing date	2016-05-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/ncomms11383
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Somatic mutations reveal asymmetric cellular dynamics in the early human embryo.

Ju, Young Seok / Martincorena, Inigo / Gerstung, Moritz / Petljak, Mia / Alexandrov, Ludmil B / Rahbari, Raheleh / Wedge, David C / Davies, Helen R / Ramakrishna, Manasa / Fullam, Anthony / Martin, Sancha / Alder, Christopher / Patel, Nikita / Gamble, Steve / O'Meara, Sarah / Giri, Dilip D / Sauer, Torril / Pinder, Sarah E / Purdie, Colin A /

Nature

2017 Volume 543, Issue 7647, Page(s) 714–718

Abstract: Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics ... ...

Abstract	Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. This study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.
MeSH term(s)	Adult ; Blood Cells/metabolism ; Cell Lineage/genetics ; Embryo, Mammalian/cytology ; Embryo, Mammalian/metabolism ; Embryonic Development/genetics ; Genome, Human/genetics ; Germ-Line Mutation/genetics ; Humans ; Mosaicism ; Mutagenesis ; Mutation ; Mutation Rate
Language	English
Publishing date	2017-03-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature21703
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 9: Show issues
Zs.MO 244: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma.

Tarpey, Patrick S / Behjati, Sam / Cooke, Susanna L / Van Loo, Peter / Wedge, David C / Pillay, Nischalan / Marshall, John / O'Meara, Sarah / Davies, Helen / Nik-Zainal, Serena / Beare, David / Butler, Adam / Gamble, John / Hardy, Claire / Hinton, Jonathon / Jia, Ming Ming / Jayakumar, Alagu / Jones, David / Latimer, Calli /

Maddison, Mark / Martin, Sancha / McLaren, Stuart / Menzies, Andrew / Mudie, Laura / Raine, Keiran / Teague, Jon W / Tubio, Jose M C / Halai, Dina / Tirabosco, Roberto / Amary, Fernanda / Campbell, Peter J / Stratton, Michael R / Flanagan, Adrienne M / Futreal, P Andrew

Nature genetics

2013 Volume 45, Issue 8, Page(s) 923–926

Abstract: Chondrosarcoma is a heterogeneous collection of malignant bone tumors and is the second most common primary malignancy of bone after osteosarcoma. Recent work has identified frequent, recurrent mutations in IDH1 or IDH2 in nearly half of central ... ...

Abstract	Chondrosarcoma is a heterogeneous collection of malignant bone tumors and is the second most common primary malignancy of bone after osteosarcoma. Recent work has identified frequent, recurrent mutations in IDH1 or IDH2 in nearly half of central chondrosarcomas. However, there has been little systematic genomic analysis of this tumor type, and, thus, the contribution of other genes is unclear. Here we report comprehensive genomic analyses of 49 individuals with chondrosarcoma (cases). We identified hypermutability of the major cartilage collagen gene COL2A1, with insertions, deletions and rearrangements identified in 37% of cases. The patterns of mutation were consistent with selection for variants likely to impair normal collagen biosynthesis. In addition, we identified mutations in IDH1 or IDH2 (59%), TP53 (20%), the RB1 pathway (33%) and Hedgehog signaling (18%).
MeSH term(s)	Bone Neoplasms/genetics ; Bone Neoplasms/metabolism ; Bone Neoplasms/pathology ; Chondrosarcoma/genetics ; Chondrosarcoma/metabolism ; Chondrosarcoma/pathology ; Collagen Type II/genetics ; Collagen Type II/metabolism ; Computational Biology ; DNA Copy Number Variations ; Databases, Genetic ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; Humans ; Mutation ; Neoplasm Grading ; Polymorphism, Single Nucleotide ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Signal Transduction
Chemical Substances	COL2A1 protein, human ; Collagen Type II ; Hedgehog Proteins ; Retinoblastoma Protein
Language	English
Publishing date	2013-06-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/ng.2668
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 46: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito