Cancer: Principles and Practice of Oncology Primer of Molecular Biology in Cancer

 
Recent scientific advances have revolutionized cancer research and practice, creating a body of molecular biology information that is important to research scientists and clinical oncologists alike. Cancer: Principles and Practice of Oncology: Primer of the Molecular Biology of Cancer, 3rd Edition, keeps you up to date with all that’s new in this rapidly changing field.

Derived from DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology – widely regarded as the definitive clinical reference in oncology – the third edition of this popular Primer provides a single-volume, highly focused reference on every important frontier in the molecular biology of cancer.

• Compiles the knowledge and experience of leading scientists and clinicians in the field.
• Provides separate chapters on each of the 18 most common cancer types, with state-of-the-art information on how molecular biology advances are impacting clinical practice.
• Includes a thorough chapter on genetic counseling and genetic testing to help you navigate the challenges and ethical dilemmas of cancer genetics.
• Covers key topics such as Hallmarks of Cancer, Precision Medicine in Oncology, Cancer Immunotherapy, Pharmacogenomics, and many more.

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Table of Contents:

1.    Contributors

2.    PART I: Principles of Molecular Oncology

3.    1. The Cancer Genome

4.    Yardena Samuels, Alberto Bardelli, Yochai Wolf, and Carlos López-Otin

5.    Introduction

6.    Cancer Genes and Their Mutations

7.    Identification of Cancer Genes

8.    Cancer Gene Discovery by Sequencing Candidate Gene Families

9.    Mutational Analysis of Exomes Using Sanger Sequencing

10.  Next-Generation Sequencing and Cancer Genome Analysis

11.  Whole-Genome Analysis Utilizing Second-Generation Sequencing

12.  Whole-Exome Analysis Utilizing Second-Generation Sequencing

13.  Somatic Alteration Classes Detected by Cancer Genome Analysis

14.  Pathway-Oriented Models of Cancer Genome Analysis

15.  Passenger and Driver Mutations

16.  Networks of Cancer Genome Projects

17.  The Genomic Landscape of Cancers

18.  Single-Cell Genomics

19.  Integrative Analysis of Cancer Genomics

20.  Immunogenomics

21.  The Cancer Genome and the New Taxonomy of Tumors

22.  Liquid Biopsies as a Diagnosis Tool

23.  Clinical Applications of Liquid Biopsies

24.  Cancer Genomics and Drug Resistance

25.  Perspectives of Cancer Genome Analysis

26.  Acknowledgments

27.  2. Molecular Methods in Cancer

28.  Larissa V. Furtado, Jay L. Hess, and Bryan L. Betz

29.  Applications of Molecular Diagnostics in Oncology

30.  Biomarker Genetics

31.  Use of Biomarkers in Diagnosis

32.  Use of Biomarkers in Prognosis

33.  Use of Biomarkers in Predicting Response to Therapy

34.  Use of Biomarkers in Therapeutic Disease Monitoring

35.  Use of Biomarkers in Risk Assessment and Cancer Prevention

36.  The Clinical Molecular Diagnostics Laboratory: Rules and Regulations

37.  Specimen Requirements for Molecular Diagnostics

38.  Molecular Diagnostics Testing Process

39.  Targeted Mutation Analysis Methods

40.  Polymerase Chain Reaction

41.  Real-time Polymerase Chain Reaction

42.  Reverse-Transcription Polymerase Chain Reaction

43.  Allele-Specific Polymerase Chain Reaction

44.  Fragment Analysis

45.  Sanger Sequencing

46.  Pyrosequencing

47.  Methylation Analysis

48.  Microsatellite Instability Analysis/Assessment of Mismatch Repair Deficiency

49.  Fluorescence In Situ Hybridization

50.  Whole-Genome Analysis Methods

51.  Next-Generation Sequencing

52.  Genomic Microarrays

53.  Expression Panels

54.  Immunohistochemistry for Tumor Biomarkers

55.  PD-L1

56.  ALK and ROS1

57.  BRAFV600E

58.  Cell-Free DNA Technologies

59.  3. Hallmarks of Cancer: An Organizing Principle for Cancer Medicine

60.  Douglas Hanahan and Robert A. Weinberg

61.  Introduction

62.  Hallmark Capabilities, In Essence

63.  Sustaining Proliferative Signaling

64.  Somatic Mutations Activate Additional Downstream Pathways

65.  Disruptions of Negative-Feedback Mechanisms that Attenuate Proliferative Signaling

66.  Excessive Proliferative Signaling Can Trigger Cell Senescence

67.  Evading Growth Suppressors

68.  Mechanisms of Contact Inhibition and Its Evasion

69.  Corruption of the Transforming Growth Factor β Pathway Promotes Malignancy

70.  Resisting Cell Death

71.  Autophagy Mediates Both Tumor Cell Survival and Death

72.  Necrosis Has Proinflammatory and Tumor-Promoting Potential

73.  Enabling Replicative Immortality

74.  Reassessing Replicative Senescence

75.  Delayed Activation of Telomerase May Both Limit and Foster Neoplastic Progression

76.  Inducing Angiogenesis

77.  Gradations of the Angiogenic Switch

78.  Endogenous Angiogenesis Inhibitors Present Natural Barriers to Tumor Angiogenesis

79.  Pericytes Are Important Components of the Tumor Neovasculature

80.  A Variety of Bone Marrow–Derived Cells Contribute to Tumor Angiogenesis

81.  Activating Invasion and Metastasis

82.  The Epithelial-to-Mesenchymal Transition Program Broadly Regulates Invasion and Metastasis

83.  Heterotypic Contributions of Stromal Cells to Invasion and Metastasis

84.  Plasticity in the Invasive Growth Program

85.  Distinct Forms of Invasion May Underlie Different Cancer Types

86.  The Daunting Complexity of Metastatic Colonization

87.  Reprogramming Energy Metabolism

88.  Evading Immune Destruction

89.  Two Ubiquitous Characteristics Facilitate the Acquisition of Hallmark Capabilities

90.  An Enabling Characteristic: Genome Instability and Mutation

91.  An Enabling Characteristic: Tumor-Promoting Inflammation

92.  The Constituent Cell Types of the Tumor Microenvironment

93.  Cancer-Associated Fibroblasts

94.  Endothelial Cells

95.  Pericytes

96.  Immune Inflammatory Cells

97.  Stem and Progenitor Cells of the Tumor Stroma

98.  Heterotypic Signaling Orchestrates the Cells of the Tumor Microenvironment

99.  Coevolution of the Tumor Microenvironment During Carcinogenesis

100.               Cancer Cells, Cancer Stem Cells, and Intratumoral Heterogeneity

101.               Therapeutic Targeting of the Hallmarks of Cancer

102.               Conclusion and a Vision for the Future

103.               Acknowledgment

104.               4. Oncogenic Viruses

105.               Christopher B. Buck, Lee Ratner, and Giovanna Tosato

106.               Principles of Tumor Virology

107.               Papillomaviruses

108.               History

109.               Tissue Tropism and Gene Functions

110.               Human Papillomavirus Vaccines

111.               Oropharyngeal Cancer

112.               Nonmelanoma Skin Cancer

113.               Bladder Cancer

114.               Polyomaviruses

115.               History

116.               BK Polyomavirus

117.               Merkel Cell Polyomavirus

118.               Other Human Polyomaviruses

119.               Epstein-Barr Virus

120.               History

121.               Epstein-Barr Virus Life Cycle

122.               Lymphomas

123.               Carcinomas

124.               Prevention and Treatment

125.               Kaposi Sarcoma Herpesvirus

126.               History and Epidemiology

127.               Kaposi Sarcoma–Associated Herpesvirus in Kaposi Sarcoma

128.               Lymphoproliferative Disorders

129.               Animal and Human Retroviruses

130.               Human T-Cell Leukemia Virus Epidemiology

131.               Human T-Cell Leukemia Virus Molecular Biology

132.               Clinical Characteristics and Treatment of Human T-lymphotropic Virus 1–Associated Malignancies

133.               Hepatitis Viruses

134.               Hepatitis B Virus

135.               Hepatitis C Virus

136.               Hepatitis Virus Pathogenesis

137.               Clinical Characteristics and Treatment of Hepatitis Virus–Associated Malignancies

138.               Conclusion

139.               5. DNA Repair in Normal and Cancer Cells

140.               Meredith A. Morgan and Theodore S. Lawrence

141.               Introduction

142.               Radiation-Induced DNA Damage

143.               Cellular Responses to Radiation-Induced DNA Damage

144.               Cell Cycle Checkpoint Pathways

145.               DNA Repair

146.               Metabolism

147.               Innate Immune Response

148.               Chromosome Aberrations Result from Faulty DNA Double-Strand Break Repair

149.               Membrane Signaling

150.               The Effect of Radiation on Cell Survival

151.               In Vivo Survival Determination of Normal Tissue Response to Radiation

152.               In Vivo Determination of Tumor Response to Radiation

153.               Factors That Affect Radiation Response

154.               The Fundamental Principles of Radiobiology

155.               Dose-Rate Effects

156.               Relative Biologic Effectiveness

157.               Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy

158.               Cell Cycle

159.               Tumor Oxygenation

160.               Immune Response

161.               Genetic Signatures

162.               Drugs That Affect Radiation Sensitivity

163.               Antimetabolites

164.               Platinums and Temozolomide

165.               Taxanes

166.               Molecularly Targeted Agents

167.               Immunotherapy

168.               Radiation Protection

169.               6. Microbiome and Cancer

170.               Giorgio Trinchieri

171.               Introduction

172.               Cancer as a Disease of the Metaorganism

173.               Bacteria as Cause of Cancer

174.               Helicobacter pylori and Stomach Cancer

175.               Colorectal Cancer

176.               Tumors in Tissues Not Directly Colonized by the Microbiota

177.               The Microbiota Modulates Cancer-Predisposing Conditions and Comorbidity

178.               Bacteria as Cancer Drugs

179.               Microbiota and Drug Metabolism

180.               Microbiota and Chemotherapy

181.               Microbiota and Immunotherapy

182.               Immune Checkpoint Blockers: Anti-CTLA-4

183.               Immune Checkpoint Blockers: Anti-PD-1/PD-L1

184.               Looking Forward

185.               7. Precision Medicine in Oncology

186.               James H. Doroshow

187.               Introduction

188.               Approach to Precision Medicine in Oncology

189.               Next-Generation DNA Sequencing for Precision Oncology

190.               Broadening the Spectrum of Molecular Characterization

191.               Preclinical Models to Inform Precision Oncology

192.               Role of Molecular Pharmacodynamics and Diagnostics in Precision Oncology

193.               Human Biospecimens for Molecular Characterization

194.               Molecular Pharmacodynamics in Precision Oncology

195.               Predictive Diagnostic Assays

196.               Precision Oncology Clinical Trials and Trial Designs

197.               Imaging and Precision Oncology

198.               Precision Prevention

199.               Future Prospects

200.               8. Cancer Immunotherapy

201.               Jeffrey Weber and Iulia Giuroiu

202.               Introduction

203.               Interferon-α

204.               Interleukin-2

205.               Talimogene Laherparepvec

206.               Granulocyte Macrophage Colony-Stimulating Factor

207.               Tumor-Infiltrating Lymphocytes

208.               Checkpoint Inhibitors—Cytotoxic T-Lymphocyte Antigen 4 and Programmed Cell Death Protein 1

209.               Cytotoxic T-Lymphocyte Antigen 4 Blockade

210.               Programmed Cell Death Protein 1 and Programmed Cell Death Protein Ligand 1 Blockade

211.               Melanoma

212.               Non–small-cell Lung Cancer

213.               Mismatch-Repair Deficient or Microsatellite Instability-High Cancers

214.               Renal Cell Carcinoma

215.               Hodgkin Lymphoma

216.               Head and Neck Squamous Cell Carcinoma

217.               Urothelial Carcinoma

218.               Merkel Cell Carcinoma

219.               Hepatocellular Carcinoma

220.               Gastric Cancer

221.               Cervical Cancer

222.               Primary Mediastinal Large B-Cell Lymphoma

223.               Dosing

224.               Vaccines

225.               Sipuleucel-T

226.               Conclusion

227.               9. Immunotherapy Agents

228.               Jeffrey A. Sosman and Douglas B. Johnson

229.               Introduction

230.               Human Tumor Antigens

231.               Mutanome-Associated Neoantigens

232.               Tumor Vaccines

233.               Personalized Neoantigen Vaccination

234.               Immune Checkpoint Inhibitors

235.               Other Immune Checkpoint Inhibitors in Development

236.               Anti-TIGIT

237.               TIM-3

238.               LAG-3

239.               KIR

240.               CD73

241.               VISTA

242.               B7-H3

243.               Immune Checkpoint Activators

244.               4-1BB (CD137)

245.               GITR

246.               ICOS

247.               CD40

248.               CD27-CD70

249.               OX40

250.               Oncolytic Viruses

251.               Talimogene Laherparepvec

252.               Other Oncolytic Viruses

253.               Factors to Activate Immune Effector Cells

254.               Cytokines

255.               IL-2 Variant Molecules

256.               Signaling Modulation

257.               STAT3 Inhibition

258.               PI3Kδ Inhibitors

259.               PI3Kγ Inhibitors

260.               Chemokine Inhibitors

261.               CXCR2 Inhibitors

262.               CCR2 Inhibitors

263.               CXCR4 Inhibitors

264.               CCR4 Antibodies

265.               CCR5 Inhibitors

266.               Soluble Factors

267.               IDO Inhibition

268.               Arginase Inhibitor

269.               TGF-β Kinase Inhibitors

270.               Adenosine A2α Receptor Axis

271.               Adenosine Receptor Inhibitors

272.               Innate Immune Modulation

273.               Pathogen-Associated Molecular Patterns, Damage-Associated Molecular Patterns, and Pattern Recognition Receptors

274.               Toll-Like Receptor Modulators

275.               STING Agonists

276.               Anti-CD47 Monoclonal Antibodies

277.               Colony-Stimulating Factor 1 Receptor Inhibition

278.               Bifunctional Fusion Proteins

279.               Immunocytokines

280.               Adoptive Cell Therapy

281.               Chimeric Antigen Receptor T-Cell Therapy

282.               10. Monoclonal Antibodies

283.               Hossein Borghaei, Matthew K. Robinson, Gregory P. Adams, and Louis M. Weiner

284.               Introduction

285.               Immunoglobulin Structure

286.               Structural and Functional Domains

287.               Modified Antibody-Based Molecules

288.               Factors Regulating Antibody-Based Tumor Targeting

289.               Antibody Size

290.               Tumor Antigens

291.               Half-Life/Clearance Rate

292.               Glycosylation

293.               Unconjugated Antibodies

294.               Cell-Mediated Cytotoxicity

295.               Complement-Dependent Cytotoxicity

296.               Altering Signal Transduction

297.               Immunoconjugates

298.               Antibody–Drug Conjugates

299.               Radioimmunoconjugates

300.               Antibodies Approved for Use in Solid Tumors

301.               Trastuzumab

302.               Pertuzumab

303.               Cetuximab

304.               Panitumumab

305.               Necitumumab

306.               Bevacizumab

307.               Ado-Trastuzumab Emtansine

308.               Ramucirumab

309.               Denosumab

310.               Antibodies Used in Hematologic Malignancies

311.               Rituximab

312.               ofatumumab

313.               Alemtuzumab

314.               Brentuximab Vedotin

315.               Inotuzumab Ozogamicin

316.               Obinutuzumab

317.               Blinatumomab

318.               Daratumumab

319.               Elotuzumab

320.               Dinutuximab

321.               Olaratumab

322.               Conclusion

323.               11. Cancer Susceptibility Syndromes

324.               Alice Hawley Berger and Pier Paolo Pandolfi

325.               Introduction

326.               Principles of Cancer Susceptibility

327.               The “Two-Hit” Paradigm

328.               What Is the Function of a Tumor Suppressor?

329.               Haploinsufficiency and Compound Haploinsufficiency

330.               Genetic Testing

331.               Cancer Susceptibility Syndromes

332.               Retinoblastoma

333.               Incidence

334.               Genetic Basis

335.               Molecular Mechanism

336.               Mouse Models

337.               Clinical Features and Therapeutic Intervention

338.               Most Prevalent Syndromes

339.               Lynch Syndrome

340.               Hereditary Breast and Ovarian Cancer

341.               Neurofibromatosis Type 1

342.               Familial Adenomatous Polyposis

343.               Other Syndromes, by Function

344.               Genomic Integrity and Apoptosis

345.               Regulation of Protein Translation

346.               Proliferation

347.               Angiogenesis

348.               Principles of Cancer Chemoprevention

349.               Emerging Knowledge and New Lessons

350.               Germline Mutations in Sporadic Cancer

351.               Weak Modifiers

352.               Epigenetic Factors

353.               Role of Noncoding RNAs

354.               The Regulatory Genome

355.               High-Throughput Methods for Understanding Cancer Variants

356.               Conclusion

357.               12. Pharmacogenomics

358.               Christine M. Walko and Howard L. McLeod

359.               Introduction

360.               Pharmacogenomics of Tumor Response

361.               Pathway-Directed Anticancer Therapy

362.               Genetic-Guided Therapy: Practical Issues in Somatic Analysis

363.               Pharmacogenomics of Chemotherapy Drug Toxicity

364.               Thiopurine Methyltransferase

365.               Dihydropyrimidine Dehydrogenase

366.               Conclusions and Future Directions

367.               13. Genetic Counseling

368.               Danielle C. Bonadies, Meagan B. Farmer, and Ellen T. Matloff

369.               Introduction

370.               Who is a Candidate for Cancer Genetic Counseling?

371.               Components of the Cancer Genetic Counseling Session

372.               Precounseling Information

373.               Family History

374.               Dysmorphology Screening

375.               Risk Assessment

376.               Genetic Testing

377.               Options for Surveillance, Risk Reduction, and Tailored Treatment

378.               Follow-up

379.               Issues in Cancer Genetic Counseling

380.               Genetic Test Selection and Approaches

381.               Management of the Patient with a Pathogenic Variant in a Moderate-Risk or Lesser Known Gene

382.               Genetic Testing in Children

383.               Reproductive Issues

384.               Potential Germline Implications of Tumor Genomic Profiling

385.               Changes in Delivery Models

386.               Direct-to-Consumer Genetic Testing

387.               Psychosocial Issues

388.               Confidentiality

389.               Insurance and Discrimination Issues

390.               Future Directions

391.               Whole-Genome Sequencing and Whole-Exome Sequencing

392.               General Population Testing

393.               CRISPR

394.               Conclusion

395.               PART II: Molecular Biology of Individual Cancers

396.               14. The Molecular Biology of Head and Neck Cancers

397.               Thomas E. Carey, Mark E. Prince, and J. Chad Brenner

398.               Incidence, Risk Factors, and Etiology

399.               Oral Tongue Cancer in Young Patients

400.               High-Risk Hpv in Oropharyngeal Cancer

401.               Molecular Mechanisms in Hnscc

402.               The Cancer Genome Atlas Project

403.               Inhibition of Hnscc Immune Escape

404.               Cancer Stem Cells

405.               15. The Molecular Biology of Lung Cancer

406.               Jill E. Larsen and John D. Minna

407.               Introduction

408.               Genomics: Tools for Identification, Prediction, and Prognosis

409.               Somatic Landscape of Lung Cancer

410.               Characterization of Aberrant Pathways

411.               Transcriptome Profiling

412.               Proteomic Approaches

413.               Lessons Learned and Future Directions

414.               Functional Genomics in Lung Cancer

415.               Genome-wide RNA-Based and shRNA-Based Screening

416.               CRISPR-Cas9 Gene Editing

417.               Preclinical Model Systems for Studying Lung Cancer

418.               Genetic and Epigenetic Alterations in Lung Cancer

419.               EGFR/HER2/MET Signaling

420.               EGFR

421.               ERBB2 (HER2)

422.               MET

423.               RAS/RAF/MAPK Pathway

424.               RAS

425.               RAF

426.               MEK (MAP2K1 or MEK1)

427.               MYC

428.               Pl3K/AKT/mTOR Pathway

429.               STK11 (LKB1)

430.               Insulin Growth Factor Pathway

431.               Fibroblast Growth Factor Pathway

432.               The p53 Pathway

433.               The p16INK4a-RB Pathway

434.               Fusion Proteins

435.               ALK

436.               ROS1

437.               RET

438.               NTRK

439.               BRAF

440.               EGFR

441.               Epigenetic Changes in Lung Carcinogenesis

442.               Methylation and Chromatin Remodeling

443.               Noncoding RNAs

444.               NFIB, a Metastasis-Inducing Transcription Factor

445.               KDM Lysine Demethylases (JumonjiC) as an Epigenomic Drug Resistance Mechanism

446.               Metastasis and the Tumor Microenvironment

447.               Epithelial-to-Mesenchymal Transition

448.               Angiogenesis

449.               Immune Checkpoint Inhibition

450.               Exosomes as a Source of Information on Tumor Molecular Alterations

451.               Lung Cancers Stem Cells

452.               Telomerase-Mediated Cellular Immortality in Lung Cancer

453.               Clinical Translation of Molecular Data

454.               Current Translation of Rationale-based Targeted Therapy

455.               Potential for Future Clinical Translation

456.               16. Molecular Biology of the Esophagus and Stomach

457.               Anil K. Rustgi

458.               Introduction

459.               Molecular Biology of Esophageal Cancer

460.               Epidermal Growth Factor Receptor

461.               Cyclin D1 and p16INK4a

462.               TP53 Tumor Suppressor Genes

463.               Telomerase Activation

464.               Tumor Invasion and Metastasis

465.               Models of Esophageal Squamous Cell Cancer and Esophageal Adenocarcinoma

466.               Functional Genomics

467.               Molecular Biology of Gastric Cancer

468.               Inherited Susceptibility

469.               Role of Helicobacter pylori Infection and Other Host–Environmental Factors

470.               Molecular Genetic Alterations

471.               Models of Gastric Cancer

472.               17. The Molecular Biology of Pancreas Cancer

473.               Scott E. Kern and Ralph H. Hruban

474.               Introduction

475.               Common Genetic Changes in Pancreatic Ductal Adenocarcinoma

476.               Less-Prevalent Genetic Changes in Pancreatic Ductal Adenocarcinoma

477.               Other Neoplastic Lesions

478.               18. Molecular Biology of Liver Cancer

479.               Jens U. Marquardt and Snorri S. Thorgeirsson

480.               Introduction

481.               Genetic Alterations in Liver Cancer

482.               Epigenetic Alterations in Liver Cancer

483.               Mutational Landscape of Genetic Alterations—The Next Generation

484.               The Microenvironment of Liver Cancer

485.               Classification and Prognostic Prediction of Hepatocellular Carcinoma

486.               Molecular Basis of Cholangiocarcinoma

487.               Conclusion and Perspective

488.               19. Molecular Biology of Colorectal Cancer

489.               Ramesh A. Shivdasani

490.               Introduction

491.               Multistep Models of Colorectal Cancer and Genetic Instability

492.               Mutational and Epigenetic Landscapes in Colorectal Cancer

493.               Insights from Mouse Intestinal Crypts and Human Colorectal Cancers Lead to a Coherent Model for Colorectal Cancer Initiation and Progression

494.               WNT Signaling

495.               Other Growth Factor Pathways

496.               Inherited Syndromes of Increased Cancer Risk Highlight Early Events and Critical Pathways in Colorectal Tumorigenesis

497.               Familial Adenomatous Polyposis and the Central Importance of WNT Signaling

498.               Hereditary Nonpolyposis Colorectal Cancer and the Role of DNA Mismatch Repair

499.               Other Inherited Syndromes with Elevated Colorectal Cancer Risk

500.               Familial Juvenile Polyposis

501.               Insights from Mendelian Syndromes, Genome-Wide Association Studies, and the Microbiome

502.               Oncogene and Tumor Suppressor Gene Mutations in Colorectal Cancer Progression

503.               The KRAS, BRAF, and PIK3CA Oncogenes

504.               MYC, CDK8, and Control of Cell Growth and Metabolism

505.               TP53 and Other Tumor Suppressors

506.               Prognostic and Predictive Value of Tumor Genotypes and Molecular Properties

507.               20. Molecular Biology of Kidney Cancer

508.               W. Marston Linehan and Laura S. Schmidt

509.               Introduction

510.               Clear Cell Renal Cell Carcinoma

511.               von Hippel-Lindau Disease

512.               Genetics of von Hippel-Lindau Disease: VHL Gene

513.               Gene Mutated in Renal Cancer Families with Chromosome 3p Translocations

514.               Sporadic Clear Cell Kidney Cancer: VHL Gene Mutation

515.               Function of the von Hippel-Lindau Protein

516.               Additional Genes Mutated in Clear Cell Kidney Cancer

517.               Papillary Renal Cell Carcinoma

518.               Hereditary Papillary Renal Carcinoma: Type 1 Papillary

519.               Genetics of Hereditary Papillary Renal Carcinoma: MET Protooncogene

520.               Hereditary Papillary Renal Carcinoma: Functional Consequences of MET Mutations

521.               Sporadic Type 1 Papillary Renal Cell Carcinoma

522.               Xp11.2 Translocation Renal Cell Cancer

523.               Hereditary Leiomyomatosis and Renal Cell Carcinoma: Type 2 Papillary

524.               Hereditary Leiomyomatosis and Renal Cell Carcinoma: Fumarate Hydratase Gene

525.               Functional Consequences of Fumarate Hydratase Mutations

526.               Sporadic Type 2 Papillary Renal Cell Carcinoma

527.               Chromophobe Renal Cell Carcinoma

528.               Birt-Hogg-Dubé Syndrome

529.               Birt-Hogg-Dubé Syndrome: FLCN Gene

530.               Function of the Birt-Hogg-Dubé Protein: Folliculin

531.               Sporadic Chromophobe Renal Cell Carcinoma

532.               Additional Types of Renal Cell Carcinoma

533.               Tuberous Sclerosis Complex

534.               Succinate Dehydrogenase–Associated Renal Cancer

535.               Conclusion

536.               21. Molecular Biology of Bladder Cancer

537.               Carolyn D. Hurst and Margaret A. Knowles

538.               Introduction

539.               Mutational Landscape

540.               Mutation Rates, Mutational Signatures, and Mutational Processes

541.               FGFR3, PIK3CA, and RAS Genes

542.               Telomerase Reverse Transcriptase Promoter

543.               TP53, RB1, and CDKN2A

544.               Genes Involved in Chromatin Modification and Architecture

545.               STAG2

546.               Alterations in DNA Repair Pathways

547.               Structural Alterations to the Genome

548.               Heterogeneity and Clonal Evolution

549.               Molecular Subtypes

550.               DNA-Based Subtypes

551.               Transcriptome-Based Subtypes

552.               Therapeutic Opportunities and Future Outlook

553.               22. The Molecular Biology of Prostate Cancer

554.               Charles Dai and Nima Sharifi

555.               Introduction

556.               The Genomic Landscape of Prostate Cancer

557.               The Molecular Subtypes of Primary Prostate Cancer

558.               ETS Family Gene Fusions

559.               Speckle-Type POZ Protein Mutations

560.               Forkhead Box A1 Mutations

561.               Serine Peptidase Inhibitor, Kazal Type 1 Overexpression

562.               Isocitrate Dehydrogenase 1 Mutations

563.               The Clonal Evolution of Lethal Metastatic Prostate Cancer

564.               Genetic Basis of Prostate Cancer Heritability

565.               Androgen Signaling in Prostate Cancer

566.               androgen Receptor Structure and Function

567.               androgen Receptor Action

568.               Intratumoral androgen Biosynthesis

569.               Glucocorticoid Signaling in Treatment Resistance

570.               Other Signaling Pathways in Prostate Cancer

571.               Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Pathway

572.               Other Signaling Pathways in Prostate Cancer

573.               Cell Cycle Aberrations

574.               Neuroendocrine Prostate Cancer

575.               Areas of Ongoing Research and Emerging Therapeutic Approaches

576.               DNA Repair Pathway

577.               Epigenetic Alterations

578.               Conclusion

579.               23. Molecular Biology of Gynecologic Cancers

580.               Tanja Pejovic, Adam J. Krieg, and Kunle Odunsi

581.               Introduction

582.               Ovarian Cancer

583.               Origins of Epithelial Ovarian Cancer

584.               Molecular Pathways to Ovarian Cancer

585.               Inherited Syndromes of Ovarian Cancers

586.               Targeting Homologous Recombination Defects in Gynecologic Cancer

587.               Ovarian Cancer Microenvironment, Metastases, and Angiogenesis

588.               Ovarian Cancer Microenvironment

589.               Angiogenesis and Tumor Hypoxia

590.               Influences of the Microenvironment on Tumor Metastasis

591.               Epigenetics

592.               Role of Specific Immune Responses and Immunotherapy

593.               Immune Inhibitory Network and Immune Checkpoint Inhibitors in Ovarian Cancer

594.               Immunotherapy Clinical Trials in Ovarian Cancer

595.               Adoptive Cellular Transfer Therapy

596.               Endometrial Cancer

597.               Type I Cancers

598.               Type II Endometrial Cancer

599.               Microsatellite Instability

600.               PTEN

601.               KRAS Mutations

602.               β-Catenin

603.               Cervix, Vaginal, and Vulvar Cancers

604.               Role of Human Papillomavirus

605.               Immune Evasion by Human Papillomavirus

606.               Human Papillomavirus Vaccines

607.               Adoptive T-Cell Therapy

608.               24. Molecular Biology of Breast Cancer

609.               Ana T. Nunes, Tara Berman, and Lyndsay Harris

610.               Introduction

611.               Genetics of Breast Cancer

612.               Hereditary Breast Cancer

613.               High-Penetrance, Low-Frequency Genes

614.               Moderate-Penetrance, Low-Frequency Genes

615.               Low-Penetrance, High-Frequency Genes and Loci

616.               Microsatellite Instability in Breast Cancer

617.               Somatic Alterations in Breast Cancer

618.               Copy Number Alterations in Breast Cancer

619.               Transcriptional Profiles of Breast Cancer—Molecular Subtypes

620.               Luminal Subtypes

621.               HER2-Enriched Subtype

622.               Triple-Negative Subtypes

623.               Mutational Profiles in Breast Cancer by Molecular Subtype

624.               Transcriptional Profiles of Breast Cancer—Prognosis and Benefit of Therapy

625.               70-Gene Assay (Mammaprint)

626.               21-Gene Recurrence Score (Oncotype DX)

627.               Prediction Analysis of Microarray-50 (PAM50, PAM50 Risk of Recurrence Score, or Prosigna)

628.               12-Gene Risk Score (Endopredict)

629.               Two-Gene Ratio (Breast Cancer Index)

630.               Epigenetics of Breast Cancer

631.               Protein/Pathway Alterations

632.               Estrogen Receptor Pathway

633.               Growth Factor Receptor Pathways

634.               Human Epidermal Growth Factor Receptor 2

635.               RAS and Phosphatidylinositol 3-Kinase Signaling Pathways

636.               Cyclin-Dependent Kinases

637.               25. Molecular Biology of Endocrine Tumors

638.               Zeyad T. Sahli, Brittany A. Avin, and Martha A. Zeiger

639.               Endocrine Syndromes

640.               Multiple Endocrine Neoplasia Type 1

641.               Clinical Features

642.               Molecular Genetics of MEN1

643.               Multiple Endocrine Neoplasia Type 2

644.               Clinical Features of MEN2A

645.               Clinical Features of MEN2B

646.               Molecular Genetics of MEN2

647.               Multiple Endocrine Neoplasia Type 4

648.               Carney Complex

649.               Clinical Features

650.               Molecular Genetics of Carney Complex

651.               Adrenal Gland

652.               Cortisol-Producing Adenomas

653.               Aldosterone-Producing Adenomas

654.               Pheochromocytoma

655.               Adrenocortical Carcinoma

656.               Parathyroid Gland

657.               Hyperparathyroidism–Jaw Tumor Syndrome

658.               Familial Hypocalciuric Hypercalcemia

659.               Neonatal Severe Hyperparathyroidism

660.               Autosomal Dominant Hypoparathyroidism

661.               Familial Isolated Hyperparathyroidism

662.               Pituitary Gland

663.               Familial Isolated Pituitary Adenoma

664.               X-linked Acrogigantism

665.               McCune-Albright Syndrome

666.               Paraganglioma, Pheochromocytoma, and Pituitary Adenoma Association

667.               Dicer1 Syndrome

668.               Thyroid Gland

669.               Follicular Adenomas

670.               Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features

671.               Papillary Thyroid Cancer

672.               Follicular Thyroid Cancer

673.               Hürthle Cell Carcinoma

674.               Medullary Thyroid Cancer

675.               Anaplastic Thyroid Cancer

676.               Werner Syndrome

677.               Acknowledgments

678.               26. Molecular Biology of Sarcomas

679.               Samuel Singer and Cristina R. Antonescu

680.               Introduction

681.               Soft Tissue Sarcomas

682.               Translocation-Associated Soft Tissue Sarcomas

683.               Myxoid/Round Cell Liposarcoma

684.               Ewing Sarcoma

685.               Desmoplastic Small Round Cell Tumor

686.               Synovial Sarcoma

687.               Alveolar Rhabdomyosarcoma

688.               Alveolar Soft Part Sarcoma

689.               Dermatofibrosarcoma Protuberans

690.               Extraskeletal Myxoid Chondrosarcoma

691.               Solitary Fibrous Tumor and Hemangiopericytoma

692.               Soft Tissue Sarcomas of Simple Karyotype Associated With Mutations

693.               Desmoid Fibromatosis

694.               Complex Soft Tissue Sarcoma Types

695.               Well-Differentiated and Dedifferentiated Liposarcoma

696.               Pleomorphic Liposarcoma

697.               Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma (Malignant Fibrous Histiocytoma)

698.               Myxofibrosarcoma

699.               Undifferentiated Pleomorphic Sarcoma (Malignant Fibrous Histiocytoma)

700.               Leiomyosarcoma

701.               Malignant Peripheral Nerve Sheath Tumor

702.               Angiosarcoma

703.               Bone and Cartilaginous Tumors

704.               Cartilaginous Tumors

705.               Enchondroma

706.               Osteochondroma

707.               Chondrosarcoma

708.               Osteosarcoma

709.               Future Directions: Next-Generation Sequencing and Functional Screens

710.               27. Molecular Biology of Cutaneous Melanoma

711.               Michael A. Davies

712.               Introduction

713.               The Cancer Genome Atlas Effort in Cutaneous Melanoma

714.               The Ras-Raf-Mapk Pathway

715.               RAF Kinases

716.               RAS Family GTPases

717.               NF1

718.               Additional Oncogenic Pathways

719.               Cell Cycle Regulators

720.               The p53 Pathway

721.               The Phosphatidylinositol 3-Kinase Pathway

722.               Receptor Tyrosine Kinases

723.               RAC1

724.               Telomerase

725.               Triple Wild-Type Melanomas

726.               Melanin Synthesis Pathway

727.               MITF

728.               The MC1R Pathway

729.               Summary and Future Directions

730.               28. Molecular Biology of Central Nervous System Tumors

731.               Mark W. Youngblood, Jennifer Moliterno Günel, and Murat Günel

732.               Introduction

733.               Pediatric Brain Tumors

734.               Medulloblastoma

735.               Low-Grade Glioma

736.               High-Grade Glioma

737.               Ependymal Tumors

738.               Adult Brain Tumors

739.               Low-Grade Glioma

740.               High-Grade Glioma

741.               Meningioma

742.               Summary

743.               Acknowledgments

744.               29. Molecular Biology of Lymphoma

745.               Nicolò Compagno, Laura Pasqualucci, and Riccardo Dalla-Favera

746.               Introduction

747.               The Cell of Origin of Lymphoma

748.               B-Cell Development and the Dynamics of the Germinal Center Reaction

749.               T-Cell Development

750.               General Mechanisms of Genetic Alterations in Lymphoma

751.               Chromosomal Translocations

752.               Aberrant Somatic Hypermutation

753.               Copy Number Gains and Amplifications

754.               Activating Point Mutations

755.               Inactivating Mutations and Deletions

756.               Infectious Agents

757.               Molecular Pathogenesis of B-Cell Non-Hodgkin Lymphoma

758.               Mantle Cell Lymphoma

759.               Cell of Origin

760.               Genetic Lesions

761.               Burkitt Lymphoma

762.               Cell of Origin

763.               Genetic Lesions

764.               Follicular Lymphoma

765.               Cell of Origin

766.               Genetic Lesions

767.               Diffuse Large B-Cell Lymphoma

768.               Cell of Origin

769.               Genetic Lesions

770.               Primary Mediastinal B-Cell Lymphoma

771.               Cell of Origin

772.               Genetic Lesions

773.               Marginal Zone Lymphoma

774.               Cell of Origin

775.               Genetic Lesions

776.               Chronic Lymphocytic Leukemia

777.               Cell of Origin

778.               Genetic Lesions

779.               Molecular Pathogenesis of T-Cell Non-Hodgkin Lymphoma

780.               Adult T-Cell Leukemia/Lymphoma (HTLV-1 Positive)

781.               Cell of Origin

782.               Genetic Lesions

783.               Angioimmunoblastic T-Cell Lymphoma

784.               Cell of Origin

785.               Genetic Lesions

786.               Peripheral T-Cell Lymphoma Not Otherwise Specified

787.               Genetic Lesions

788.               Cutaneous T-Cell Lymphoma

789.               Anaplastic Large-Cell Lymphoma

790.               Cell of Origin

791.               Genetic Lesions

792.               Hepatosplenic T-Cell Lymphoma

793.               Molecular Pathogenesis of Hodgkin Lymphoma

794.               Cell of Origin

795.               Genetic Lesions

796.               30. Molecular Biology of Acute Leukemias

797.               Glen D. Raffel and Jan Cerny

798.               Introduction

799.               Leukemic Stem Cell

800.               Elucidation of Genetic Events in Acute Leukemia

801.               Mutations Affecting Transcription Factors

802.               Core-Binding Factor

803.               Retinoic Acid Receptor Alpha Gene

804.               HOX Family Members

805.               C/EBPα

806.               GATA Factors

807.               Mutations that Result in Overexpression of c-MYC

808.               Mutation of Lymphoid Development Factors in Acute Lymphoid Leukemia

809.               Chromosomal Translocations Involving the T-cell Receptor

810.               RBM15/MKL1

811.               Mutations of Epigenetic Modifiers

812.               KMT2A (aka MLL) Translocations

813.               MOZ and TIF2

814.               TET2

815.               DNMT3A

816.               ASXL1

817.               EZH2

818.               Mutations Affecting Signaling

819.               Oncogenic RAS Mutations

820.               Activating Mutations in Tyrosine Kinases and Associated Receptors

821.               BCR/ABL1

822.               FLT3

823.               KIT

824.               MPL

825.               JAK/STAT Pathway

826.               CRLF2

827.               Kinases in Ph-Negative Acute Lymphoid Leukemia

828.               Mutations in Tumor Suppressor Genes

829.               WT1

830.               TP53

831.               Activating Mutations of Notch

832.               Mutations Altering Localization of Npm1

833.               Mutations in Cohesin Complex Genes

834.               Mutations in Splicing Machinery

835.               Mutational Complementation Groups in Acute Leukemias

836.               Conclusion

837.               31. Molecular Biology of Chronic Leukemias

838.               Christopher A. Eide, James S. Blachly, and Anupriya Agarwal

839.               Introduction

840.               Chronic Myeloid Leukemia

841.               Pathogenesis

842.               Molecular Anatomy of the BCR-ABL1 Junction

843.               Functional Domains of BCR-ABL1 and Kinase Activation

844.               Signal Transduction

845.               Phosphatidylinositol-3 Kinase

846.               Rat Sarcoma/Mitogen-Activated Protein Kinase Pathways

847.               Janus Kinase/Signal Transducer and Activator of Transcription Pathway

848.               DNA Repair

849.               Chronic Myeloid Leukemia Stem Cells

850.               Progression to Blastic Phase

851.               Chronic Myeloid Leukemia Bone Marrow Microenvironment

852.               Conclusions

853.               Chronic Lymphocytic Leukemia

854.               Origin of Chronic Lymphocytic Leukemia

855.               Chromosomal Abnormalities in the Pathogenesis of Chronic Lymphocytic Leukemia

856.               Recurrent Mutations in Chronic Lymphocytic Leukemia

857.               Progression of Chronic Lymphocytic Leukemia: The Role of Genomic Instability and Clonal Evolution

858.               Chronic Lymphocytic Leukemia and Proliferation

859.               Chronic Lymphocytic Leukemia and Disrupted Apoptosis

860.               B-cell Receptor Signaling in Chronic Lymphocytic Leukemia

861.               Conclusion

862.               Acknowledgments

863.               Index

 

An aparitie	6 April 2020
Autor	Vincent T. DeVita Jr. MD, Theodore S. Lawrence, Steven A. Rosenberg
Dimensiuni	15.3 x 22.9 cm
Editura	Lippincott Williams and Wilkins
Format	Paperback
ISBN	9781975149116
Limba	Engleza
Nr pag	824