scholarly journals Mice with gene alterations in the GH and IGF family

Pituitary ◽  
2021 ◽  
Author(s):  
Yanrong Qian ◽  
Darlene E. Berryman ◽  
Reetobrata Basu ◽  
Edward O. List ◽  
Shigeru Okada ◽  
...  
Keyword(s):  
Gene Alterations

Gene Alterations and Apoptosis in Rhabdomyosarcoma

1997 ◽  
Vol 17 (2) ◽  
pp. 233-247
Author(s):  
Francoise Boman ◽  
Didier Brel ◽  
Laurent Antunes ◽  
Zaitouna Alhamany ◽  
Jean Floquet ◽  
...  
Keyword(s):  
Gene Alterations

scholarly journals The CRISPR/Cas9 Minipig—A Transgenic Minipig to Produce Specific Mutations in Designated Tissues

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3024
Author(s):  
Martin Fogtmann Berthelsen ◽  
Maria Riedel ◽  
Huiqiang Cai ◽  
Søren H. Skaarup ◽  
Aage K. O. Alstrup ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Somatic Cells ◽  
Genetic Alterations ◽  
Lung Epithelial Cells ◽  
Target Cells ◽  
Multiple Gene ◽  
Conditional Expression ◽  
Gene Alterations

The generation of large transgenic animals is impeded by complex cloning, long maturation and gastrulation times. An introduction of multiple gene alterations increases the complexity. We have cloned a transgenic Cas9 minipig to introduce multiple mutations by CRISPR in somatic cells. Transgenic Cas9 pigs were generated by somatic cell nuclear transfer and were backcrossed to Göttingen Minipigs for two generations. Cas9 expression was controlled by FlpO-mediated recombination and was visualized by translation from red to yellow fluorescent protein. In vitro analyses in primary fibroblasts, keratinocytes and lung epithelial cells confirmed the genetic alterations executed by the viral delivery of single guide RNAs (sgRNA) to the target cells. Moreover, multiple gene alterations could be introduced simultaneously in a cell by viral delivery of sgRNAs. Cells with loss of TP53, PTEN and gain-of-function mutation in KRASG12D showed increased proliferation, confirming a transformation of the primary cells. An in vivo activation of Cas9 expression could be induced by viral delivery to the skin. Overall, we have generated a minipig with conditional expression of Cas9, where multiple gene alterations can be introduced to somatic cells by viral delivery of sgRNA. The development of a transgenic Cas9 minipig facilitates the creation of complex pre-clinical models for cancer research.

scholarly journals O12-1 A novel gene-prediction model, virtual sequencing with deep learning to predict gene alterations in colorectal cancer

2021 ◽  
Vol 32 ◽  
pp. S290
Author(s):  
Daisuke Kotani ◽  
Satoshi Fujii ◽  
Tomoyuki Yamada ◽  
Mizuto Suzuki ◽  
Takayuki Yoshino
Keyword(s):  
Colorectal Cancer ◽  
Deep Learning ◽  
Prediction Model ◽  
Gene Prediction ◽  
Novel Gene ◽  
Gene Alterations

scholarly journals ARID2 Chromatin Remodeler in Hepatocellular Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2152
Author(s):  
Robin Loesch ◽  
Linda Chenane ◽  
Sabine Colnot
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Associated Factors ◽  
Regulation Of Gene Expression ◽  
Specific Gene ◽  
Chromatin Remodeler ◽  
Chromatin Remodelers ◽  
Genes Encoding ◽  
Gene Alterations

Chromatin remodelers are found highly mutated in cancer including hepatocellular carcinoma. These mutations frequently occur in ARID (AT-rich Interactive Domain) genes, encoding subunits of the ATP-dependent SWI/SNF remodelers. The increasingly prevalent complexity that surrounds the functions and specificities of the highly modular BAF (BG1/BRM-associated factors) and PBAF (polybromo-associated BAF) complexes, including ARID1A/B or ARID2, is baffling. The involvement of the SWI/SNF complexes in diverse tissues and processes, and especially in the regulation of gene expression, multiplies the specific outcomes of specific gene alterations. A better understanding of the molecular consequences of specific mutations impairing chromatin remodelers is needed. In this review, we summarize what we know about the tumor-modulating properties of ARID2 in hepatocellular carcinoma.

scholarly journals A Methodological Framework to Discover Pharmacogenomic Interactions Based on Random Forests

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 933
Author(s):  
Salvatore Fasola ◽  
Giovanna Cilluffo ◽  
Laura Montalbano ◽  
Velia Malizia ◽  
Giuliana Ferrante ◽  
...  
Keyword(s):  
Random Forests ◽  
Cancer Cell Line ◽  
Predictive Performance ◽  
Computational Time ◽  
Gene Interactions ◽  
Methodological Framework ◽  
Concordance Correlation ◽  
Driver Genes ◽  
Tumor Tissues ◽  
Gene Alterations

The identification of genomic alterations in tumor tissues, including somatic mutations, deletions, and gene amplifications, produces large amounts of data, which can be correlated with a diversity of therapeutic responses. We aimed to provide a methodological framework to discover pharmacogenomic interactions based on Random Forests. We matched two databases from the Cancer Cell Line Encyclopaedia (CCLE) project, and the Genomics of Drug Sensitivity in Cancer (GDSC) project. For a total of 648 shared cell lines, we considered 48,270 gene alterations from CCLE as input features and the area under the dose-response curve (AUC) for 265 drugs from GDSC as the outcomes. A three-step reduction to 501 alterations was performed, selecting known driver genes and excluding very frequent/infrequent alterations and redundant ones. For each model, we used the concordance correlation coefficient (CCC) for assessing the predictive performance, and permutation importance for assessing the contribution of each alteration. In a reasonable computational time (56 min), we identified 12 compounds whose response was at least fairly sensitive (CCC > 20) to the alteration profiles. Some diversities were found in the sets of influential alterations, providing clues to discover significant drug-gene interactions. The proposed methodological framework can be helpful for mining pharmacogenomic interactions.

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