Principles of cancer genetics:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Dordrecht ; Heidelberg ; New York ; London
Springer
[2016]
|
| Ausgabe: | Second edition |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | xii, 343 Seiten Illustrationen, Diagramme |
| ISBN: | 9789401774826 |
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Datensatz im Suchindex
| _version_ | 1804176375299440640 |
|---|---|
| adam_text | Titel: Principles of cancer genetics
Autor: Bunz, Fred
Jahr: 2016
Contents
1 The Genetic Basis of Cancer........................................................................................................................................1
The Cancer Gene Theory........................................................................................................................................................1
Cancers Are Invasive Ttimors..........................................................................................................................................2
Cancer Is a Unique Type of Genetic Disease............................................................................................3
What Are Cancer Genes and How Are They Acquired?........................................................4
Mutations Alter the Human Genome....................................................................................................................5
Genes and Mutations......................................................................................................................................................................7
Single Nucleotide Substitutions....................................................................................................................................13
Gene Silencing Is Marked by Cytosine Methylation: Epigenetics..........................16
Environmental Mutagens, Mutations and Cancer..............................................................................17
Inflammation Promotes the Propagation of Cancer Genes..................................................22
Stem Cells, Darwinian Selection and the Clonal
Evolution of Cancers......................................................................................................................................................................25
Selective Pressure and Adaptation: Hypoxia
and Altered Metabolism............................................................................................................................................................28
Multiple Somatic Mutations Punctuate Clonal Evolution....................................................30
Tumor Growth Leads to Cellular Heterogeneity..................................................................................31
Tumors Are Distinguished by Their Spectrum of Driver
Gene Mutations and Passenger Gene Mutations..................................................................................33
Colorectal Cancer: A Model for Understanding the Process
of Ttimorigenesis..................................................................................................................................................................................33
Do Cancer Cells Divide More Rapidly Than Normal Cells?............................................37
Germline Cancer Genes Allow Neoplasia to Bypass Steps
in Clonal Evolution..........................................................................................................................................................................38
Cancer Syndromes Reveal Rate-Limiting Steps
in Ttimorigenesis..................................................................................................................................................................................40
The Etiologic Triad: Heredity, the Environment,
and Stem Cell Division..............................................................................................................................................................43
Understanding Cancer Genetics....................................................................................................................................45
Further Reading....................................................................................................................................................................................46
vii
viii Contents
2 Oncogenes.......................................... ................................................................................................................47
What Is An Oncogene?..............................................................................................................................................................47
The Discovery of Transmissible Cancer Genes....................................................................................47
Viral Oncogenes Are Derived from the Host Genome..............................................................50
The Search for Activated Oncogenes: The RAS Gene Family......................................52
Complex Genomic Rearrangements: The MYC Gene Family......................................55
Proto-oncogene Activation by Gene Amplification........................................................................56
Proto-oncogenes Can Be Activated by Chromosomal Translocation..................60
Chromosomal Translocations in Liquid Tumors................................................................................60
Chronic Myeloid Leukemia and the Philadelphia Chromosome................................61
Oncogenic Activation of Transcription Factors
in Prostate Cancer and Ewing s Sarcoma......................................................................................................65
Oncogene Discovery in the Genomic Era: Mutations in PIK3CA............................67
Selection of Tumor-Associated Mutations....................................................................................................69
Multiple Modes of Proto-oncogene Activation......................................................................................70
Oncogenes Are Dominant Cancer Genes...........................................................................71
Germline Mutations in RET and MET Confer Cancer Predisposition................72
Proto-oncogene Activation and Tumorigenesis....................................................................................73
Further Reading....................................................................................................................................................................................74
3 Ihmor Suppressor Genes..................................................................................................................................................75
What Is a Tumor Suppressor Gene?........................................................................................................................75
The Discovery of Recessive Cancer Phenotypes................................................................................76
Retinoblastoma and Knudson s Two-Hit Hypothesis..................................................................77
Chromosomal Localization of the Retinoblastoma Gene......................................................80
The Mapping and Cloning of the Retinoblastoma Gene........................................................82
Tumor Suppressor Gene Inactivation: The Second Hit and Loss
of Heterozygosity................................................................................................................................................................................85
Recessive Genes, Dominant Traits............................................................................................................................87
APC Inactivation in Inherited and Sporadic Colorectal Cancers................................88
TP53 Inactivation: A Frequent Event in Tumorigenesis..........................................................91
Functional Inactivation of p53: Tumor Suppressor
Genes and Oncogenes Interact........................................................................................................................................93
Mutant TP53 in the Germline: Li-Fraumeni Syndrome..........................................................94
Gains-of-Function Caused by
Cancer-Associated Mutations in TP53..............................................................................................................98
Cancer Predisposition: Allelic Penetrance,
Relative Risk and the Odds Ratio..............................................................................................................................99
Breast Cancer Susceptibility: BRCAl and BRCA2..........................................................................104
Genetic Losses on Chromosome 9: CDKN2A........................................................................................108
Complexity at CDKN2A: Neighboring
and Overlapping Genes..............................................................................................................................................................Ill
Genetic Losses on Chromosome 10: PTEN................................................................................................113
SMAD4 and the Maintenance of Stromal Architecture..............................................................116
Contents ix
Two Distinct Genes Cause Neurofibromatosis........................................... 119
From Flies to Humans, Patched Proteins Regulate
Developmental Morphogenesis................................................................... 121
von Hippel-Lindau Disease......................................................................... 122
NOTCH1: Tumor Suppressor Gene or Oncogene?..........................................................................122
Multiple Endocrine Neoplasia Type 1................................................................................................................123
Most Tumor Suppressor Genes Are Tissue-Specific....................................................................124
Modeling Cancer Syndromes in Mice................................................................................................................126
Genetic Variation and Germline Cancer Genes....................................................................................128
Tumor Suppressor Gene Inactivation During
Colorectal Tbmorigenesis......................................................................................................................................................130
Inherited Tumor Suppressor Gene Mutations:
Gatekeepers and Landscapers..........................................................................................................................................132
Maintaining the Genome: Caretakers..................................................................................................................133
Further Reading....................................................................................................................................................................................133
4 Genetic Instability and Cancer................................................................................................................................135
What Is Genetic Instability?................................................................................................................................................135
The Majority of Cancer Cells Are Aneuploid..........................................................................................136
Aneuploid Cancer Cells Exhibit Chromosome Instability....................................................138
Chromosome Instability Arises Early in Colorectal Tumorigenesis......................140
Chromosomal Instability Accelerates Clonal Evolution..........................................................141
Aneuploidy Can Result from Mutations
That Directly Impact Mitosis............................................................................................................................................143
STAG2 and the Cohesion of Sister Chromatids....................................................................................144
Other Genetic and Epigenetic Causes of Aneuploidy..................................................................146
Transition from Tetraploidy to Aneuploidy
During Thmorigenesis..................................................................................................................................................................148
Multiple Forms of Genetic Instability in Cancer................................................................................149
Defects in Mismatch Repair Cause Hereditary
Nonpolyposis Colorectal Cancer................................................................................................................................151
Mismatch Repair-Deficient Cancers Have
a Distinct Spectrum of Mutations..............................................................................................................................157
Defects in Nucleotide Excision Repair
Cause Xeroderma Pigmentosum..................................................................................................................................158
NER Syndromes: Clinical Heterogeneity and Pleiotropy......................................................163
DNA Repair Defects and Mutagens Define
Two Steps Towards Genetic Instability..............................................................................................................166
Defects in DNA Crosslink Repair Cause Fanconi Anemia................................................167
A Defect in DNA Double Strand Break
Responses Causes Ataxia-Telangiectasia........................................................................................................172
A Unique Form of Genetic Instability
Underlies Bloom Syndrome................................................................................................................................................175
Aging and Cancer: Insights from the Progeroid Syndromes............................................179
Instability at the End: Telomeres and Telomerase............................................................................182
x Contents
Overview: Genes and Genetic Stability............................................................................................................184
Further Reading....................................................................................................................................................................................185
5 Cancer Genomes..............................................................................................................................................................................187
Discovering the Genetic Basis of Cancer: From Genes to Genomes..................187
What Types of Genetic Alterations Are Found in Tumor Cells?................................188
How Many Genes Are Mutated in the Various Types of Cancer?............................188
What Is the Significance of the Mutations
That Are Found in Cancers?..............................................................................................................................................191
When Do Cancer-Associated Mutations Occur?................................................................................193
How Many Different Cancer Genes Are There?..................................................................................194
How Many Cancer Genes Are Required
for the Development of Cancer?..................................................................................................................................195
Cancer Genetics Shapes Our Understanding of Metastasis................................................195
Tumors Are Genetically Heterogenous..............................................................................................................197
Beyond the Exome: The Dark Matter of the Cancer Genome..................................199
A Summary: The Genome of a Cancer Cell..............................................................................................200
Further Reading......................................................................................................200
6 Cancer Gene Pathways..........................................................................................................................................................203
What Are Cancer Gene Pathways?..........................................................................................................................203
Cellular Pathways Are Defined by Protein-Protein Interactions................................205
Individual Biochemical Reactions, Multistep
Pathways, and Networks..........................................................................................................................................................207
Protein Phosphorylation Is a Common Regulatory Mechanism..................................210
Signals from the Cell Surface: Protein Tyrosine Kinases......................................................212
Membrane-Associated GTPases: The RAS Pathway..................................................................217
An Intracellular Kinase Cascade: The MAPK Pathway..........................................................219
Genetic Alterations of the RAS Pathway in Cancer......................................................................219
Membrane-Associated Lipid Phosphorylation:
The PI3K/AKT Pathway..........................................................................................................................................................221
Control of Cell Growth and Energetics: The mTOR Pathway........................................224
Genetic Alterations in the PI3K/AKT
and mTOR Pathways Define Roles in Cell Survival......................................................................225
The STAT Pathway Transmits Cytokine
Signals to the Cell Nucleus..................................................................................................................................................227
Morphogenesis and Cancer: The WNT/APC Pathway..............................................................229
Dysregulation of the WNT/APC Pathway in Cancers................................................................231
Notch Signaling Mediates Cell-to-Cell Communication........................................................233
Morphogenesis and Cancer: The Hedgehog Pathway................................................................234
TGF-0/ SMAD Signaling Maintains Adult Tissue Homeostasis................................236
MYC Is a Downstream Effector of Multiple
Cancer Gene Pathways................................................................................................................................................................239
p53 Activation Is Triggered by Damaged or
Incompletely Replicated Chromosomes..........................................................................................................242
Contents xi
p53 Is Controlled by Protein Kinases Encoded
by Tumor Suppressor Genes..............................................................................................................................................244
p53 Induces the Transcription of Genes
That Suppress Cancer Phenotypes............................................................................................................................247
Feedback Loops Dynamically Control p53 Abundance..........................................................250
The DNA Damage Signaling Network Activates
Interconnected Repair Pathways..................................................................................................................................252
Inactivation of the Pathways to Apoptosis in Cancer..................................................................254
RB1 and the Regulation of the Cell Cycle....................................................................................................257
Several Cancer Gene Pathways Converge on Cell Cycle Regulators..................261
Many Cancer Cells Are Cell Cycle Checkpoint-Deficient..................................................263
Chromatin Modification Is Recurrently
Altered in Many Types of Cancer..............................................................................................................................264
Summary: Putting Together the Puzzle..............................................................................................................266
Further Reading....................................................................................................................................................................................268
7 Genetic Alternations in Common Cancers..........................................................................................271
Cancer Genes Cause Diverse Diseases..............................................................................................................271
Cancer Incidence and Prevalence................................................................................................................................272
Lung Cancer................................................................................................................................................................................................274
Prostate Cancer......................................................................................................................................................................................276
Breast Cancer............................................................................................................................................................................................278
Colorectal Cancer................................................................................................................................................................................280
Endometrial Cancer........................................................................................................................................................................282
Melanoma of the Skin..................................................................................................................................................................283
Bladder Cancer........................................................................................................................................................................................285
Lymphoma....................................................................................................................................................................................................286
Cancers in the Kidney..................................................................................................................................................................288
Thyroid Cancer......................................................................................................................................................................................289
Leukemia..........................................................................................................................................................................................................290
Cancer in the Pancreas................................................................................................................................................................292
Ovarian Cancer......................................................................................................................................................................................294
Cancers of the Oral Cavity and Pharynx..........................................................................................................295
Liver Cancer................................................................................................................................................................................................297
Cancer of the Uterine Cervix............................................................................................................................................298
Stomach Cancer....................................................................................................................................................................................299
Brain Thmors............................................................................................................................................................................................300
Further Reading....................................................................................................................................................................................302
8 Cancer Genetics in the Clinic......................................................................................................................................305
The Uses of Genetic Information................................................................................................................................305
Elements of Cancer Risk: Carcinogens and Genes..........................................................................306
Identifying Carriers of Germline Cancer Genes..................................................................................307
Cancer Genes as Biomarkers of Early Stage Malignancies................................................310
Cancer Genes as Biomarkers for Diagnosis,
Prognosis and Recurrence......................................................................................................................................................313
xii Contents
Conventional Anticancer Therapies Inhibit Cell Growth......................................................316
Exploiting the Loss of DNA Repair Pathways:
Synthetic Lethality............................................................................................................................................................................317
On the Horizon: Achieving Synthetic Lethality
in TP55-Mutant Cancers..........................................................................................................................................................319
Molecularly Targeted Therapy: BCR-ABL and Imatinib........................................................320
Clonal Evolution of Therapeutic Resistance..............................................................................................324
Targeting EGFR Mutations..................................................................................................................................................325
Antibody-Mediated Inhibition of Receptor Tyrosine Kinases........................................327
Inhibiting Hedgehog Signaling......................................................................................................................................328
A Pipeline from Genetically-Defined Targets to Targeted Therapies..................330
Neoantigens Are Recognized by the Immune System................................................................332
The Future of Oncology............................................................................................................................................................334
Futher Reading........................................................................................................................................................................................335
Index
337
|
| any_adam_object | 1 |
| author | Bunz, Fred ca. 20./21. Jh |
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| building | Verbundindex |
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| classification_rvk | WG 7000 XH 5200 |
| ctrlnum | (OCoLC)946034682 (DE-599)BVBBV043637243 |
| dewey-full | 614.5999 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 614 - Forensic medicine; incidence of disease |
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| dewey-tens | 610 - Medicine and health |
| discipline | Biologie Medizin |
| edition | Second edition |
| format | Book |
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| indexdate | 2024-07-10T07:31:11Z |
| institution | BVB |
| isbn | 9789401774826 |
| language | English |
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| physical | xii, 343 Seiten Illustrationen, Diagramme |
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| spelling | Bunz, Fred ca. 20./21. Jh. Verfasser (DE-588)1301056235 aut Principles of cancer genetics Fred Bunz Second edition Dordrecht ; Heidelberg ; New York ; London Springer [2016] xii, 343 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Medicine Cancer research Human genetics Oncology Biomedicine Cancer Research Human Genetics Medizin Krebs Medizin (DE-588)4073781-0 gnd rswk-swf Genetik (DE-588)4071711-2 gnd rswk-swf Krebs Medizin (DE-588)4073781-0 s Genetik (DE-588)4071711-2 s 1\p DE-604 Erscheint auch als Online-Ausgabe 978-94-017-7484-0 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029051145&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Bunz, Fred ca. 20./21. Jh Principles of cancer genetics Medicine Cancer research Human genetics Oncology Biomedicine Cancer Research Human Genetics Medizin Krebs Medizin (DE-588)4073781-0 gnd Genetik (DE-588)4071711-2 gnd |
| subject_GND | (DE-588)4073781-0 (DE-588)4071711-2 |
| title | Principles of cancer genetics |
| title_auth | Principles of cancer genetics |
| title_exact_search | Principles of cancer genetics |
| title_full | Principles of cancer genetics Fred Bunz |
| title_fullStr | Principles of cancer genetics Fred Bunz |
| title_full_unstemmed | Principles of cancer genetics Fred Bunz |
| title_short | Principles of cancer genetics |
| title_sort | principles of cancer genetics |
| topic | Medicine Cancer research Human genetics Oncology Biomedicine Cancer Research Human Genetics Medizin Krebs Medizin (DE-588)4073781-0 gnd Genetik (DE-588)4071711-2 gnd |
| topic_facet | Medicine Cancer research Human genetics Oncology Biomedicine Cancer Research Human Genetics Medizin Krebs Medizin Genetik |
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