LIVIVO - Search results -

Search results

Result 1 - 10 of total 16

Search options

Article ; Online ; Conference proceedings: 104th American Association For Cancer Research (AACR) annual meeting; breakthroughs in science and technology changing cancer care.

Abaan, Ogan D / Bilke, Sven

ACS chemical biology

2013 Volume 8, Issue 6, Page(s) 1097–1100

MeSH term(s)	Genome-Wide Association Study/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Neoplasms/epidemiology ; Neoplasms/genetics ; Precision Medicine/methods ; United States
Language	English
Publishing date	2013
Publishing country	United States
Document type	Congresses
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/cb400366r
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: PTPL1: a large phosphatase with a split personality.

Abaan, Ogan D / Toretsky, Jeffrey A

Cancer metastasis reviews

2008 Volume 27, Issue 2, Page(s) 205–214

Abstract: Protein tyrosine phosphatase, PTPL1, (also known as PTPN13, FAP-1, PTP-BAS, PTP1E) is a non-receptor type PTP and, at 270 kDa, is the largest phosphatase within this group. In addition to the well-conserved PTP domain, PTPL1 contains at least 7 putative ... ...

Abstract	Protein tyrosine phosphatase, PTPL1, (also known as PTPN13, FAP-1, PTP-BAS, PTP1E) is a non-receptor type PTP and, at 270 kDa, is the largest phosphatase within this group. In addition to the well-conserved PTP domain, PTPL1 contains at least 7 putative macromolecular interaction domains. This structural complexity indicates that PTPL1 may modulate diverse cellular functions, perhaps exerting both positive and negative effects. In accordance with this idea, while certain studies suggest that PTPL1 can act as a tumor-promoting gene other experimental studies have suggested that PTPL1 may function as a tumor suppressor. The role of PTPL1 in the cancer cell is therefore likely to be both complex and context dependent with possible roles including the modulation of growth, stress-response, and cytoskeletal remodeling pathways. Understanding the nature of molecular complexes containing PTPL1, its interaction partners, substrates, regulation and subcellular localization are key to unraveling the complex personality of this protein phosphatase.
MeSH term(s)	Animals ; Cell Transformation, Neoplastic ; Humans ; Oncogene Proteins/physiology ; Protein Tyrosine Phosphatase, Non-Receptor Type 13/physiology ; Tumor Suppressor Proteins/physiology
Chemical Substances	Oncogene Proteins ; Tumor Suppressor Proteins ; PTPN13 protein, human (EC 3.1.3.48) ; Protein Tyrosine Phosphatase, Non-Receptor Type 13 (EC 3.1.3.48)
Language	English
Publishing date	2008-02-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	604857-2
ISSN	1573-7233 ; 0167-7659
ISSN (online)	1573-7233
ISSN	0167-7659
DOI	10.1007/s10555-008-9114-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1812: 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)

Order via subito

Details ▾

Article: Valosin containing protein (VCP/p97) is a novel substrate for the protein tyrosine phosphatase PTPL1

Abaan, Ogan D / Hendriks, Wiljan / Üren, Aykut / Toretsky, Jeffrey A / Erkizan, Hayriye V

Experimental cell research. 2013 Jan. 1, v. 319, no. 1

2013

Abstract: Identification of Protein Tyrosine Phosphatase (PTP) substrates is critical in understanding cellular role in normal cells as well as cancer cells. We have previously shown that reduction of PTPL1 protein levels in Ewings sarcoma (ES) inhibit cell growth ...

Abstract	Identification of Protein Tyrosine Phosphatase (PTP) substrates is critical in understanding cellular role in normal cells as well as cancer cells. We have previously shown that reduction of PTPL1 protein levels in Ewings sarcoma (ES) inhibit cell growth and tumorigenesis. Therefore, we sought to identify novel PTPL1 substrates that may be important for tumorigenesis. In this current work, we demonstrated that mouse embryonic fibroblasts without PTPL1 catalytic activity fail to form foci when transfected with oncogenes. We proved that catalytic activity of PTPL1 is important for ES cell growth. Using a substrate-trapping mutant of PTPL1 we identified putative PTPL1 substrates by mass-spectrometry. One of these putative substrates was characterized as Valosin Containing Protein (VCP/p97). Using multiple biochemical assays we validated VCP as a novel substrate of PTPL1. We also provide evidence that tyrosine phosphorylation of VCP might be important for its midbody localization during cytokinesis. In conclusion, our work identifies VCP as a new substrate for PTPL1, which may be important in cellular transformation. Our investigation link an oncogenic transcription factor EWS-FLI1, with a key transcriptional target protein tyrosine phosphatase PTPL1, and its substrate VCP. Given our observation that PTPL1 catalytic activity is important for cell transformation, our results may also suggest that VCP regulation by PTPL1 might be important for tumorigenesis.
Keywords	carcinogenesis ; catalytic activity ; cell growth ; cytokinesis ; fibroblasts ; mass spectrometry ; mice ; mutants ; neoplasm cells ; oncogenes ; phosphorylation ; protein-tyrosine-phosphatase ; sarcoma ; transcription (genetics) ; transcription factors ; tyrosine
Language	English
Dates of publication	2013-0101
Size	p. 1-11.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2012.09.003
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 53/186: Show issues

Order via subito

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.

Details ▾
- See ZB MED holdings
- Order with fees

Article: miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.

Gindin, Yevgeniy / Jiang, Yuan / Francis, Princy / Walker, Robert L / Abaan, Ogan D / Zhu, Yuelin J / Meltzer, Paul S

Frontiers in genetics

2015 Volume 6, Page(s) 233

Abstract: Osteosarcoma is the most common type of bone cancer in children and adolescents. Impaired differentiation of osteoblast cells is a distinguishing feature of this aggressive disease. As improvements in survival outcomes have largely plateaued, better ... ...

Abstract	Osteosarcoma is the most common type of bone cancer in children and adolescents. Impaired differentiation of osteoblast cells is a distinguishing feature of this aggressive disease. As improvements in survival outcomes have largely plateaued, better understanding of the bone differentiation program may provide new treatment approaches. The miRNA cluster miR-23a~27a~24-2, particularly miR-23a, has been shown to interact with genes important for bone development. However, global changes in gene expression associated with functional gain of this cluster have not been fully explored. To better understand the relationship between miR-23a expression and bone cell differentiation, we carried out a large-scale gene expression analysis in HOS cells. Experimental results demonstrate that over-expression of miR-23a delays differentiation in this system. Downstream bioinformatic analysis identified miR-23a target gene connexin-43 (Cx43/GJA1), a mediator of intercellular signaling critical to osteoblast development, as acutely affected by miR-23a levels. Connexin-43 is up-regulated in the course of HOS cell differentiation and is down-regulated in cells transfected with miR-23a. Analysis of gene expression data, housed at Gene Expression Omnibus, reveals that Cx43 is consistently up-regulated during osteoblast differentiation. Suppression of Cx43 mRNA by miR-23a was confirmed in vitro using a luciferase reporter assay. This work demonstrates novel interactions between microRNA expression, intercellular signaling and bone differentiation in osteosarcoma.
Language	English
Publishing date	2015-07-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2015.00233
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Valosin containing protein (VCP/p97) is a novel substrate for the protein tyrosine phosphatase PTPL1.

Abaan, Ogan D / Hendriks, Wiljan / Uren, Aykut / Toretsky, Jeffrey A / Erkizan, Hayriye V

Experimental cell research

2012 Volume 319, Issue 1, Page(s) 1–11

Abstract	Identification of Protein Tyrosine Phosphatase (PTP) substrates is critical in understanding cellular role in normal cells as well as cancer cells. We have previously shown that reduction of PTPL1 protein levels in Ewings sarcoma (ES) inhibit cell growth and tumorigenesis. Therefore, we sought to identify novel PTPL1 substrates that may be important for tumorigenesis. In this current work, we demonstrated that mouse embryonic fibroblasts without PTPL1 catalytic activity fail to form foci when transfected with oncogenes. We proved that catalytic activity of PTPL1 is important for ES cell growth. Using a substrate-trapping mutant of PTPL1 we identified putative PTPL1 substrates by mass-spectrometry. One of these putative substrates was characterized as Valosin Containing Protein (VCP/p97). Using multiple biochemical assays we validated VCP as a novel substrate of PTPL1. We also provide evidence that tyrosine phosphorylation of VCP might be important for its midbody localization during cytokinesis. In conclusion, our work identifies VCP as a new substrate for PTPL1, which may be important in cellular transformation. Our investigation link an oncogenic transcription factor EWS-FLI1, with a key transcriptional target protein tyrosine phosphatase PTPL1, and its substrate VCP. Given our observation that PTPL1 catalytic activity is important for cell transformation, our results may also suggest that VCP regulation by PTPL1 might be important for tumorigenesis.
MeSH term(s)	Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/metabolism ; Animals ; Bone Neoplasms/enzymology ; Bone Neoplasms/pathology ; Catalysis ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Cells, Cultured ; Fibroblasts ; HEK293 Cells ; Humans ; Mice ; Mice, Mutant Strains ; Pancreatic Neoplasms/enzymology ; Pancreatic Neoplasms/pathology ; Protein Tyrosine Phosphatase, Non-Receptor Type 13/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 13/metabolism ; Sarcoma, Ewing/enzymology ; Sarcoma, Ewing/pathology ; Substrate Specificity/physiology ; Valosin Containing Protein
Chemical Substances	Cell Cycle Proteins ; Protein Tyrosine Phosphatase, Non-Receptor Type 13 (EC 3.1.3.48) ; Ptpn13 protein, mouse (EC 3.1.3.48) ; Adenosine Triphosphatases (EC 3.6.1.-) ; VCP protein, human (EC 3.6.4.6) ; Valosin Containing Protein (EC 3.6.4.6) ; Vcp protein, mouse (EC 3.6.4.6)
Language	English
Publishing date	2012-09-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2012.09.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 563: 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)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Epigenetic and genetic inactivation of tyrosyl-DNA-phosphodiesterase 1 (TDP1) in human lung cancer cells from the NCI-60 panel.

Gao, Rui / Das, Benu Brata / Chatterjee, Raghunath / Abaan, Ogan D / Agama, Keli / Matuo, Renata / Vinson, Charles / Meltzer, Paul S / Pommier, Yves

DNA repair

2013 Volume 13, Page(s) 1–9

Abstract: Tyrosyl-DNA-phosphodiesterase 1 (TDP1) repairs 3'-blocking DNA lesions by catalytically hydrolyzing the tyrosyl-DNA-phosphodiester bond of trapped topoisomerase I (Top1) cleavage complexes (Top1cc). It also removes 3'-blocking residues derived from ... ...

Abstract	Tyrosyl-DNA-phosphodiesterase 1 (TDP1) repairs 3'-blocking DNA lesions by catalytically hydrolyzing the tyrosyl-DNA-phosphodiester bond of trapped topoisomerase I (Top1) cleavage complexes (Top1cc). It also removes 3'-blocking residues derived from oxidative damage or incorporation of chain terminating anticancer and antiviral nucleosides. Thus, TDP1 is regarded as a determinant of resistance to Top1 inhibitors and chain terminating nucleosides, and possibly of genomic stability. In the 60 cell lines of the NCI Developmental Therapeutic Anticancer Screen (the NCI-60), whose whole genome transcriptome and mutations have recently been characterized, we discovered two human lung cancer cell lines deficient for TDP1 (NCI_H522 and HOP_62). HOP_62 shows undetectable TDP1 mRNA and NCI_H522 bears a homozygous deleterious mutation of TDP1 at a highly conserved amino acid residue (K292E). Absence of TDP1 protein and lack of TDP1 catalytic activity were demonstrated in cell lysates from both cell lines. Lack of TDP1 expression in HOP_62 was shown to be due to TDP1 promoter hypermethylation. Our study provides insights into the possible inactivation of TDP1 in cancers and its relationship to cellular response to Top1-targeted drugs. It also reveals two TDP1 knockout lung cancer cell lines for further TDP1 functional analyses.
MeSH term(s)	Amino Acid Sequence ; Cell Line, Tumor ; Conserved Sequence ; DNA Methylation ; DNA Topoisomerases, Type I/genetics ; DNA Topoisomerases, Type I/metabolism ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/genetics ; Mutation ; National Cancer Institute (U.S.) ; Phosphoric Diester Hydrolases/genetics ; Phosphoric Diester Hydrolases/metabolism ; Promoter Regions, Genetic ; United States
Chemical Substances	Phosphoric Diester Hydrolases (EC 3.1.4.-) ; TDP1 protein, human (EC 3.1.4.-) ; DNA Topoisomerases, Type I (EC 5.99.1.2) ; TOP1 protein, human (EC 5.99.1.2)
Language	English
Publishing date	2013-12-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2071608-4
ISSN	1568-7856 ; 1568-7864
ISSN (online)	1568-7856
ISSN	1568-7864
DOI	10.1016/j.dnarep.2013.09.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5555: 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: NCI-60 whole exome sequencing and pharmacological CellMiner analyses.

Reinhold, William C / Varma, Sudhir / Sousa, Fabricio / Sunshine, Margot / Abaan, Ogan D / Davis, Sean R / Reinhold, Spencer W / Kohn, Kurt W / Morris, Joel / Meltzer, Paul S / Doroshow, James H / Pommier, Yves

PloS one

2014 Volume 9, Issue 7, Page(s) e101670

Abstract: Exome sequencing provides unprecedented insights into cancer biology and pharmacological response. Here we assess these two parameters for the NCI-60, which is among the richest genomic and pharmacological publicly available cancer cell line databases. ... ...

Abstract	Exome sequencing provides unprecedented insights into cancer biology and pharmacological response. Here we assess these two parameters for the NCI-60, which is among the richest genomic and pharmacological publicly available cancer cell line databases. Homozygous genetic variants that putatively affect protein function were identified in 1,199 genes (approximately 6% of all genes). Variants that are either enriched or depleted compared to non-cancerous genomes, and thus may be influential in cancer progression and differential drug response were identified for 2,546 genes. Potential gene knockouts are made available. Assessment of cell line response to 19,940 compounds, including 110 FDA-approved drugs, reveals ≈80-fold range in resistance versus sensitivity response across cell lines. 103,422 gene variants were significantly correlated with at least one compound (at p<0.0002). These include genes of known pharmacological importance such as IGF1R, BRAF, RAD52, MTOR, STAT2 and TSC2 as well as a large number of candidate genes such as NOM1, TLL2, and XDH. We introduce two new web-based CellMiner applications that enable exploration of variant-to-compound relationships for a broad range of researchers, especially those without bioinformatics support. The first tool, "Genetic variant versus drug visualization", provides a visualization of significant correlations between drug activity-gene variant combinations. Examples are given for the known vemurafenib-BRAF, and novel ifosfamide-RAD52 pairings. The second, "Genetic variant summation" allows an assessment of cumulative genetic variations for up to 150 combined genes together; and is designed to identify the variant burden for molecular pathways or functional grouping of genes. An example of its use is provided for the EGFR-ERBB2 pathway gene variant data and the identification of correlated EGFR, ERBB2, MTOR, BRAF, MEK and ERK inhibitors. The new tools are implemented as an updated web-based CellMiner version, for which the present publication serves as a compendium.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Base Sequence ; Cell Line, Tumor ; Computational Biology/methods ; Data Mining/methods ; Databases, Factual ; Exome/genetics ; Genetic Variation/genetics ; Genome/genetics ; Genomics/methods ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Sequence Analysis, DNA
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2014-07-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0101670
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

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: High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias.

Waterfall, Joshua J / Arons, Evgeny / Walker, Robert L / Pineda, Marbin / Roth, Laura / Killian, J Keith / Abaan, Ogan D / Davis, Sean R / Kreitman, Robert J / Meltzer, Paul S

Nature genetics

2013 Volume 46, Issue 1, Page(s) 8–10

Abstract: To understand the genetic mechanisms driving variant and IGHV4-34-expressing hairy-cell leukemias, we performed whole-exome sequencing of leukemia samples from ten affected individuals, including six with matched normal samples. We identified activating ... ...

Abstract	To understand the genetic mechanisms driving variant and IGHV4-34-expressing hairy-cell leukemias, we performed whole-exome sequencing of leukemia samples from ten affected individuals, including six with matched normal samples. We identified activating mutations in the MAP2K1 gene (encoding MEK1) in 5 of these 10 samples and in 10 of 21 samples in a validation set (overall frequency of 15/31), suggesting potential new strategies for treating individuals with these diseases.
MeSH term(s)	Connectin/genetics ; DNA-Binding Proteins ; Gene Rearrangement, B-Lymphocyte, Heavy Chain/genetics ; Humans ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Variable Region/genetics ; Leukemia, Hairy Cell/genetics ; MAP Kinase Kinase 1/genetics ; Mutation Rate ; Nuclear Proteins/genetics ; Ribonucleoproteins/genetics ; Splicing Factor U2AF ; Transcription Factors/genetics ; Tumor Suppressor Protein p53/genetics
Chemical Substances	ARID1A protein, human ; Connectin ; DNA-Binding Proteins ; Immunoglobulin Heavy Chains ; Immunoglobulin Variable Region ; Nuclear Proteins ; Ribonucleoproteins ; Splicing Factor U2AF ; TP53 protein, human ; TTN protein, human ; Transcription Factors ; Tumor Suppressor Protein p53 ; U2AF1 protein, human ; MAP Kinase Kinase 1 (EC 2.7.12.2) ; MAP2K1 protein, human (EC 2.7.12.2)
Language	English
Publishing date	2013-11-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; 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.2828
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: Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing.

Fang, Li Tai / Zhu, Bin / Zhao, Yongmei / Chen, Wanqiu / Yang, Zhaowei / Kerrigan, Liz / Langenbach, Kurt / de Mars, Maryellen / Lu, Charles / Idler, Kenneth / Jacob, Howard / Zheng, Yuanting / Ren, Luyao / Yu, Ying / Jaeger, Erich / Schroth, Gary P / Abaan, Ogan D / Talsania, Keyur / Lack, Justin /

Shen, Tsai-Wei / Chen, Zhong / Stanbouly, Seta / Tran, Bao / Shetty, Jyoti / Kriga, Yuliya / Meerzaman, Daoud / Nguyen, Cu / Petitjean, Virginie / Sultan, Marc / Cam, Margaret / Mehta, Monika / Hung, Tiffany / Peters, Eric / Kalamegham, Rasika / Sahraeian, Sayed Mohammad Ebrahim / Mohiyuddin, Marghoob / Guo, Yunfei / Yao, Lijing / Song, Lei / Lam, Hugo Y K / Drabek, Jiri / Vojta, Petr / Maestro, Roberta / Gasparotto, Daniela / Kõks, Sulev / Reimann, Ene / Scherer, Andreas / Nordlund, Jessica / Liljedahl, Ulrika / Jensen, Roderick V / Pirooznia, Mehdi / Li, Zhipan / Xiao, Chunlin / Sherry, Stephen T / Kusko, Rebecca / Moos, Malcolm / Donaldson, Eric / Tezak, Zivana / Ning, Baitang / Tong, Weida / Li, Jing / Duerken-Hughes, Penelope / Catalanotti, Claudia / Maheshwari, Shamoni / Shuga, Joe / Liang, Winnie S / Keats, Jonathan / Adkins, Jonathan / Tassone, Erica / Zismann, Victoria / McDaniel, Timothy / Trent, Jeffrey / Foox, Jonathan / Butler, Daniel / Mason, Christopher E / Hong, Huixiao / Shi, Leming / Wang, Charles / Xiao, Wenming

Nature biotechnology

2021 Volume 39, Issue 9, Page(s) 1151–1160

Abstract: The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets ... ...

Abstract	The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.
MeSH term(s)	Benchmarking ; Breast Neoplasms/genetics ; Cell Line, Tumor ; DNA Mutational Analysis/standards ; Datasets as Topic ; Germ Cells ; High-Throughput Nucleotide Sequencing/standards ; Humans ; Mutation ; Reference Standards ; Reproducibility of Results ; Whole Genome Sequencing/standards
Language	English
Publishing date	2021-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1311932-1
ISSN	1546-1696 ; 1087-0156
ISSN (online)	1546-1696
ISSN	1087-0156
DOI	10.1038/s41587-021-00993-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2167: 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.MO 137: Show issues
Zs.MG 43: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: NCI-60 whole exome sequencing and pharmacological CellMiner analyses.

William C Reinhold / Sudhir Varma / Fabricio Sousa / Margot Sunshine / Ogan D Abaan / Sean R Davis / Spencer W Reinhold / Kurt W Kohn / Joel Morris / Paul S Meltzer / James H Doroshow / Yves Pommier

PLoS ONE, Vol 9, Iss 7, p e

2014 Volume 101670

Abstract	Exome sequencing provides unprecedented insights into cancer biology and pharmacological response. Here we assess these two parameters for the NCI-60, which is among the richest genomic and pharmacological publicly available cancer cell line databases. Homozygous genetic variants that putatively affect protein function were identified in 1,199 genes (approximately 6% of all genes). Variants that are either enriched or depleted compared to non-cancerous genomes, and thus may be influential in cancer progression and differential drug response were identified for 2,546 genes. Potential gene knockouts are made available. Assessment of cell line response to 19,940 compounds, including 110 FDA-approved drugs, reveals ≈80-fold range in resistance versus sensitivity response across cell lines. 103,422 gene variants were significantly correlated with at least one compound (at p<0.0002). These include genes of known pharmacological importance such as IGF1R, BRAF, RAD52, MTOR, STAT2 and TSC2 as well as a large number of candidate genes such as NOM1, TLL2, and XDH. We introduce two new web-based CellMiner applications that enable exploration of variant-to-compound relationships for a broad range of researchers, especially those without bioinformatics support. The first tool, "Genetic variant versus drug visualization", provides a visualization of significant correlations between drug activity-gene variant combinations. Examples are given for the known vemurafenib-BRAF, and novel ifosfamide-RAD52 pairings. The second, "Genetic variant summation" allows an assessment of cumulative genetic variations for up to 150 combined genes together; and is designed to identify the variant burden for molecular pathways or functional grouping of genes. An example of its use is provided for the EGFR-ERBB2 pathway gene variant data and the identification of correlated EGFR, ERBB2, MTOR, BRAF, MEK and ERK inhibitors. The new tools are implemented as an updated web-based CellMiner version, for which the present publication serves as a compendium.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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.

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

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

Inter-library loan at ZB MED

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

Full text online

More links

Kategorien

Inter-library loan at ZB MED