: Adam J. Dupuy, David A. Largaespada
: Adam J. Dupuy, David A. Largaespada
: Insertional Mutagenesis Strategies in Cancer Genetics
: Springer-Verlag
: 9781441976567
: 1
: CHF 85.20
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: Nichtklinische Fächer
: English
: 200
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The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.

Adam Dupuy, Ph.D., is an Assistant Professor at the Carver College of Medicine at the University of Iowa, and a rising star in the field of insertional mutagenesis; two of the last of his publications have been in Nature, and he was the lead author on one of these. Dr. Dupuy earned his B.A. at Central College in Pella, Iowar, went on to earn his Ph.D. at the University of Minnesota in the Program in Molecular, Cellular, Developmental Biology& Genetics, and did his Postdoctoral fellowship in the Mouse Cancer Genetics Program at the NCI-Frederick.

Contents5
Contributors6
1 Insertional Mutagenesis: A Powerful Tool in Cancer Research8
1.1 Introduction8
1.2 Historical Perspective9
1.3 The Site of Insertion can Provide Mechanistic Insights11
1.4 Methodologies12
1.5 Pairing Insertional Mutagenesis with Other Genetic Tools15
1.6 Mining Hidden Information in Mutagenesis Screens17
1.7 Importance of Thorough Bioinformatics Analysis19
1.8 The Added Value of Large Numbers20
1.9 Crossvalidation with Other Genetic Datasets20
1.10 Are New Cancer Causing Pathways to be Found21
1.11 Conclusions and Recommendations22
References23
2 Retroviral Insertional Mutagenesis in Mouse Models of Leukemia and Lymphoma26
2.1 Introduction to the Murine Leukemia Viruses26
2.2 Viral and Host Determinants of Disease28
2.3 Challenges in MLV Mutagenesis Studies30
2.4 Comparative Oncogenomics36
2.5 Validation of Candidates38
2.6 Do Murine Retroviruses Cause Human Cancer40
2.7 Summary and Future Perspectives40
References41
3 Gene Discovery by MMTV Mediated Insertional Mutagenesis46
3.1 Introduction46
3.1.1 Mouse Mammary Gland Biology48
3.1.2 Mouse Mammary Tumor Virus48
3.1.3 Viral Genes and Genomic Organization50
3.1.4 Transcription and Translation of the Viral Genes51
3.1.5 Virion Structure and Assembly52
3.1.6 Infectious Life Cycle53
3.1.7 Tissue Specificity and Hormonal Regulation of MMTV Replication54
3.1.8 Exogenous MMTV55
3.1.9 Endogenous MMTV56
3.1.10 MMTV-Induced Tumors56
3.1.11 MMTV Induced Hormone Dependent Premalignant Lesions57
3.1.12 Hormone-Dependent Mammary Tumors and MMTV58
3.1.13 MMTV-Induced Tumors in other Tissues58
3.2 Gene Discovery by MMTV Mediated Insertional Mutagenesis59
3.2.1 Common Integration Sites59
3.2.2 Modes by Which Insertional Mutagenesis Affects Cancer Genes60
3.3