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Talk: The genetic basis of kidney cancer (52 min)

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X Navigable Slide Index
  1. Introduction
  2. Renal carcinoma
  3. Stage I kidney cancer
  4. Stage IV kidney cancer
  5. Human renal epithelial neoplasms
  6. Loss of alleles in renal cell carcinoma
  7. Mapping the minimal 3p loss region
  8. Studying cancer families to identify genes
  9. Identification of kidney cancer genes
  10. Inherited forms of renal carcinoma
  11. von Hippel Lindau (VHL) CCRC
  12. VHL clinical features
  13. VHL: renal cell carcinoma
  14. VHL: multiple clear cell renal carcinomas
  15. VHL-associated RCC high persistence rate
  16. VHL: advanced RCC
  17. NCI VHL kindreds
  18. VHL: surgical management
  19. NIH clinical center (1)
  20. Genetic analysis of VHL families
  21. VHL gene is on chromosome 3
  22. VHL gene localization map
  23. Human VHL gene
  24. Germline VHL mutations
  25. NCI VHL germline mutations
  26. VHL gene: sporadic RCC
  27. Sporadic clear cell RCC VHL gene mutations
  28. Clear cell renal carcinoma
  29. Papillary renal carcinoma
  30. VHL is a two hit loss of function tumor suppressor
  31. VHL -/- athymic nude mice
  32. Mouse with RCC + VHL gene
  33. How does the VHL gene function?
  34. Degradation of HIF alpha
  35. Downstream effects of VHL mutation
  36. Targeting VHL/HIF in clear cell RCC
  37. TCGA clear cell kidney cancer
  38. Intratumor Heterogeneity
  39. Intratumor heterogeneity: implications for therapy
  40. Warburg effect in clear cell kidney cancer
  41. Non-clear cell RCC
  42. Locally advanced kidney cancer
  43. Papillary kidney cancer: patient 1 (pathology)
  44. Papillary kidney cancer: patient 2
  45. Papillary kidney cancer: patient 2 (pathology)
  46. Papillary kidney cancer: patient 3A
  47. Papillary kidney cancer: patient 3B
  48. Papillary kidney cancer: patient 3C
  49. Papillary kidney cancer patient 3 (pathology)
  50. Hereditary papillary renal carcinoma (HPRC)
  51. Inherited renal carcinoma
  52. HPRC: renal tumors
  53. Hereditary papillary renal carcinoma type 1
  54. Penetrance of MET mutation H1210R
  55. HPRC: high prevalence
  56. HPRC: surgical management
  57. NIH clinical center (2)
  58. MET gene is on chromosome 7
  59. Location of the HPRC gene
  60. MET is the HPRC gene
  61. HPRC: mutations in the tyrosine kinase domain
  62. Location of MET mutations in HPRC patients
  63. NCI HPRC kindreds
  64. Early onset HPRC
  65. Targeting MET RCC gene pathway
  66. Potential small molecule target
  67. Foretinib: dual VEGFR and MET inhibitor
  68. MiT kidney cancer TFE3, TFEB, MITF
  69. Back to locally advanced kidney cancer patient
  70. Samples from patient
  71. UOK124: papillary kidney cancer cell line
  72. TFE3 kidney cancer
  73. TFE3 kidney cancer epidemiology
  74. Microphthalmia transcription factor (MITF)
  75. TFEB kidney cancer patient 1
  76. TFEB kidney cancer patient 2
  77. TFE3 translocation kidney cancer patient
  78. TFE3 translocation patient (lymph node spread)
  79. Inherited renal carcinoma Birt-Hogg-Dube (BHD)
  80. BHD cutaneous manifestations (obvious)
  81. BHD cutaneous manifestations (subtle)
  82. Kidney tumors in BHD
  83. Kidney tumors in BHD (solitary)
  84. Kidney tumors in BHD (bi-lateral)
  85. Kidney tumors in BHD (spread)
  86. Different cancer types in BHD
  87. BHD renal tumor pathology
  88. BHD: surgical management
  89. BHD lung cysts (patient 1)
  90. BHD lung cysts (patient 2)
  91. BHD lung cysts (patient 3)
  92. Identification of the BHD gene
  93. NIH Clinical Center (3)
  94. Cutaneous fibrofolliculomas as a marker
  95. BHD gene is on chromosome 17
  96. BHD gene locus
  97. BHD protein sequence
  98. FLCN mutation spectrum
  99. FLCN Mutation analysis
  100. What kind of gene is FLCN?
  101. BHD gene analysis in BHD-associated RCC
  102. Somatic mutations in BHD renal tumors
  103. Mutations in tumors from a single BHD patient
  104. BHD -/- RCC cell line is tumorigenic
  105. BHD restored RCC cell line is not tumorigenic
  106. How does the FLCN gene function?
  107. Folliculin-FNIP1/2-AMPK interactions
  108. mTORC1/mTORC2 activation
  109. BHD deletion specifically in the kidney
  110. BHDf/d/KSPCre mouse kidney histology
  111. BHD deletion specifically in the kidney - survival
  112. Rapamycin treatment
  113. mTORC1/mTORC2 activation - treatment
  114. Young patient had HLRCC kidney cancer
  115. HLRCC kidney cancer in patient's family
  116. Inherited renal carcinoma (HLRCC)
  117. features of HLRCC
  118. HLRCC kindred
  119. HLRCC: cutaneous manifestations
  120. HLRCC: uterine leiomyomas
  121. HLRCC kidney cancer (patient 1)
  122. HLRCC kidney cancer (patient 2)
  123. HLRCC renal mass (patient 2)
  124. HLRCC kidney cancer: papillary type 2
  125. HLRCC: orangophilic nucleoli + perinucleolar halos
  126. HLRCC: occurrence in young patients
  127. HLRCC: occurrence in elderly patients
  128. 7mm HLRCC renal tumor (1)
  129. 7mm HLRCC renal tumor (2)
  130. 7mm HLRCC renal tumor (3)
  131. HLRCC patient - no tumors in 2003
  132. HLRCC patient - no tumors in 2006
  133. HLRCC patient - large tumor in 2010 (1)
  134. HLRCC patient - large tumor in 2010 (2)
  135. HLRCC patient - tumor removal and metastasis
  136. HLRCC: surgical management
  137. Fumarate hydratase gene is on chromosome 1
  138. Fumarate hydratase (FH): HLRCC gene
  139. HLRCC: mutation analysis
  140. FH is a two hit loss of function tumor suppressor
  141. UOK-262 EV (empty vector) treated mouse
  142. UOK-262 FHWT (WT replaced) treated mouse
  143. Loss of a Krebs cycle enzyme and kidney cancer
  144. Impaired citric acid cycle and “Warburg effect”
  145. HLRCC-renal cancer: glucose-dependent
  146. HLRCC tumors in vivo detection (patient 1)
  147. HLRCC tumors in vivo detection (patient 2)
  148. HLRCC retroperitoneal tumor: PET scan
  149. HLRCC chest tumor: PET scan
  150. HLRCC patient with cutaneous leioymyoma
  151. Cutaneous leioymyomas in vivo detection
  152. Uterine leiomyomas
  153. Krebs cycle modifications
  154. HLRCC novel treatment approaches
  155. HLRCC: effects of increased fumarate
  156. Summary of kidney cancer pathology
  157. Kidney cancer is a metabolic disease
  158. Acknowledgements
  159. Urologic Oncology Branch NCI
  160. END
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DETAILED SLIDE INDEX

  1. 1. Introduction
  2. 2. Renal carcinoma
  3. 3. Stage I kidney cancer
  4. 4. Stage IV kidney cancer
  5. 5. Human renal epithelial neoplasms
  6. 6. Loss of alleles in renal cell carcinoma
  7. 7. Mapping the minimal 3p loss region
  8. 8. Studying cancer families to identify genes
  9. 9. Identification of kidney cancer genes
  10. 10. Inherited forms of renal carcinoma
  11. 11. von Hippel Lindau (VHL) CCRC
  12. 12. VHL clinical features
  13. 13. VHL: renal cell carcinoma
  14. 14. VHL: multiple clear cell renal carcinomas
  15. 15. VHL-associated RCC high persistence rate
  16. 16. VHL: advanced RCC
  17. 17. NCI VHL kindreds
  18. 18. VHL: surgical management
  19. 19. NIH clinical center (1)
  20. 20. Genetic analysis of VHL families
  21. 21. VHL gene is on chromosome 3
  22. 22. VHL gene localization map
  23. 23. Human VHL gene
  24. 24. Germline VHL mutations
  25. 25. NCI VHL germline mutations
  26. 26. VHL gene: sporadic RCC
  27. 27. Sporadic clear cell RCC VHL gene mutations
  28. 28. Clear cell renal carcinoma
  29. 29. Papillary renal carcinoma
  30. 30. VHL is a two hit loss of function tumor suppressor
  31. 31. VHL -/- athymic nude mice
  32. 32. Mouse with RCC + VHL gene
  33. 33. How does the VHL gene function?
  34. 34. Degradation of HIF alpha
  35. 35. Downstream effects of VHL mutation
  36. 36. Targeting VHL/HIF in clear cell RCC
  37. 37. TCGA clear cell kidney cancer
  38. 38. Intratumor Heterogeneity
  39. 39. Intratumor heterogeneity: implications for therapy
  40. 40. Warburg effect in clear cell kidney cancer
  41. 41. Non-clear cell RCC
  42. 42. Locally advanced kidney cancer
  43. 43. Papillary kidney cancer: patient 1 (pathology)
  44. 44. Papillary kidney cancer: patient 2
  45. 45. Papillary kidney cancer: patient 2 (pathology)
  46. 46. Papillary kidney cancer: patient 3A
  47. 47. Papillary kidney cancer: patient 3B
  48. 48. Papillary kidney cancer: patient 3C
  49. 49. Papillary kidney cancer patient 3 (pathology)
  50. 50. Hereditary papillary renal carcinoma (HPRC)
  51. 51. Inherited renal carcinoma
  52. 52. HPRC: renal tumors
  53. 53. Hereditary papillary renal carcinoma type 1
  54. 54. Penetrance of MET mutation H1210R
  55. 55. HPRC: high prevalence
  56. 56. HPRC: surgical management
  57. 57. NIH clinical center (2)
  58. 58. MET gene is on chromosome 7
  59. 59. Location of the HPRC gene
  60. 60. MET is the HPRC gene
  61. 61. HPRC: mutations in the tyrosine kinase domain
  62. 62. Location of MET mutations in HPRC patients
  63. 63. NCI HPRC kindreds
  64. 64. Early onset HPRC
  65. 65. Targeting MET RCC gene pathway
  66. 66. Potential small molecule target
  67. 67. Foretinib: dual VEGFR and MET inhibitor
  68. 68. MiT kidney cancer TFE3, TFEB, MITF
  69. 69. Back to locally advanced kidney cancer patient
  70. 70. Samples from patient
  71. 71. UOK124: papillary kidney cancer cell line
  72. 72. TFE3 kidney cancer
  73. 73. TFE3 kidney cancer epidemiology
  74. 74. Microphthalmia transcription factor (MITF)
  75. 75. TFEB kidney cancer patient 1
  76. 76. TFEB kidney cancer patient 2
  77. 77. TFE3 translocation kidney cancer patient
  78. 78. TFE3 translocation patient (lymph node spread)
  79. 79. Inherited renal carcinoma Birt-Hogg-Dube (BHD)
  80. 80. BHD cutaneous manifestations (obvious)
  81. 81. BHD cutaneous manifestations (subtle)
  82. 82. Kidney tumors in BHD
  83. 83. Kidney tumors in BHD (solitary)
  84. 84. Kidney tumors in BHD (bi-lateral)
  85. 85. Kidney tumors in BHD (spread)
  86. 86. Different cancer types in BHD
  87. 87. BHD renal tumor pathology
  88. 88. BHD: surgical management
  89. 89. BHD lung cysts (patient 1)
  90. 90. BHD lung cysts (patient 2)
  91. 91. BHD lung cysts (patient 3)
  92. 92. Identification of the BHD gene
  93. 93. NIH Clinical Center (3)
  94. 94. Cutaneous fibrofolliculomas as a marker
  95. 95. BHD gene is on chromosome 17
  96. 96. BHD gene locus
  97. 97. BHD protein sequence
  98. 98. FLCN mutation spectrum
  99. 99. FLCN Mutation analysis
  100. 100. What kind of gene is FLCN?
  101. 101. BHD gene analysis in BHD-associated RCC
  102. 102. Somatic mutations in BHD renal tumors
  103. 103. Mutations in tumors from a single BHD patient
  104. 104. BHD -/- RCC cell line is tumorigenic
  105. 105. BHD restored RCC cell line is not tumorigenic
  106. 106. How does the FLCN gene function?
  107. 107. Folliculin-FNIP1/2-AMPK interactions
  108. 108. mTORC1/mTORC2 activation
  109. 109. BHD deletion specifically in the kidney
  110. 110. BHDf/d/KSPCre mouse kidney histology
  111. 111. BHD deletion specifically in the kidney - survival
  112. 112. Rapamycin treatment
  113. 113. mTORC1/mTORC2 activation - treatment
  114. 114. Young patient had HLRCC kidney cancer
  115. 115. HLRCC kidney cancer in patient's family
  116. 116. Inherited renal carcinoma (HLRCC)
  117. 117. features of HLRCC
  118. 118. HLRCC kindred
  119. 119. HLRCC: cutaneous manifestations
  120. 120. HLRCC: uterine leiomyomas
  121. 121. HLRCC kidney cancer (patient 1)
  122. 122. HLRCC kidney cancer (patient 2)
  123. 123. HLRCC renal mass (patient 2)
  124. 124. HLRCC kidney cancer: papillary type 2
  125. 125. HLRCC: orangophilic nucleoli + perinucleolar halos
  126. 126. HLRCC: occurrence in young patients
  127. 127. HLRCC: occurrence in elderly patients
  128. 128. 7mm HLRCC renal tumor (1)
  129. 129. 7mm HLRCC renal tumor (2)
  130. 130. 7mm HLRCC renal tumor (3)
  131. 131. HLRCC patient - no tumors in 2003
  132. 132. HLRCC patient - no tumors in 2006
  133. 133. HLRCC patient - large tumor in 2010 (1)
  134. 134. HLRCC patient - large tumor in 2010 (2)
  135. 135. HLRCC patient - tumor removal and metastasis
  136. 136. HLRCC: surgical management
  137. 137. Fumarate hydratase gene is on chromosome 1
  138. 138. Fumarate hydratase (FH): HLRCC gene
  139. 139. HLRCC: mutation analysis
  140. 140. FH is a two hit loss of function tumor suppressor
  141. 141. UOK-262 EV (empty vector) treated mouse
  142. 142. UOK-262 FHWT (WT replaced) treated mouse
  143. 143. Loss of a Krebs cycle enzyme and kidney cancer
  144. 144. Impaired citric acid cycle and “Warburg effect”
  145. 145. HLRCC-renal cancer: glucose-dependent
  146. 146. HLRCC tumors in vivo detection (patient 1)
  147. 147. HLRCC tumors in vivo detection (patient 2)
  148. 148. HLRCC retroperitoneal tumor: PET scan
  149. 149. HLRCC chest tumor: PET scan
  150. 150. HLRCC patient with cutaneous leioymyoma
  151. 151. Cutaneous leioymyomas in vivo detection
  152. 152. Uterine leiomyomas
  153. 153. Krebs cycle modifications
  154. 154. HLRCC novel treatment approaches
  155. 155. HLRCC: effects of increased fumarate
  156. 156. Summary of kidney cancer pathology
  157. 157. Kidney cancer is a metabolic disease
  158. 158. Acknowledgements
  159. 159. Urologic Oncology Branch NCI
  160. 160. END

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TALK'S CITATION

Linehan, W.M. (2014), "The genetic basis of kidney cancer", in Maher, E.R. (ed.), Molecular Genetics of Human Disease: , The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/?t=BL1853817)

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ABOUT THIS TALK

Speaker(s)

Dr. W. Marston Linehan Show Biography

SPEAKER BIOGRAPHY

Dr. W. Marston Linehan – National Institutes of Health, USA

W. Marston Linehan, M.D. is Chief of Urologic Surgery and the Urologic Oncology Branch, Center for Cancer Research, at the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. He received his internship, residency and fellowship training at Duke University Medical Center and then began his career at the National Cancer Institute in 1982. He has had a long standing interest in identification of the genetic basis of cancer of the kidney. By studying patients and families with kidney cancer, he and his colleagues have identified the genes involved in many different types of renal carcinoma, as well as describing five new diseases. This work has provided the basis for the development of new therapeutic strategies for the different types of kidney cancer based on understanding the molecular pathway of the specific cancer genes associated with the different types of kidney cancer. Dr. Linehan is a member of the Institute of Medicine of the National Academy of Science and is or has been on the editorial board of 14 journals. He has received the Joseph H. Burchenal Memorial Award for Outstanding Achievement in Clinical Cancer Research from the American Association of Cancer Research, the Dr. Nathan Davis Award from the American Medical Association, the Lila Gruber Award for Cancer Research from the American Association of Dermatology, the NIH Director’s Award for discovery of the VHL kidney cancer gene, the Barringer Medal from the American Association of Genitourinary Surgeons, the Gold Cystoscope Award and the Distinguished Contribution Award from the American Urological Association, the Huggins Medal and the SUO Medal from the Society of Urologic Oncology and the Andrew C. Novick Award from the Kidney Cancer Association.

Publication Date

September, 2014

Topics Covered

Renal Carcinoma... more

TOPICS COVERED IN THIS TALK

  • Renal Carcinoma
  • Stage I , Stage IV kidney cancer
  • Human Renal Epithelial Neoplasms
  • Loss of alleles in renal cell carcinoma
  • Mapping the Minimal 3p Loss Region in Clear Cell Renal Carcinoma
  • Studying Cancer Families to Identify Renal Carcinoma Genes
  • Identification of Kidney Cancer Genes
  • Inherited Forms of Renal Carcinoma
  • Clear Cell Renal Carcinoma: von Hippel Lindau (VHL)
  • VHL Gene
  • VHL Gene Localization Map
  • Germline VHL Mutations
  • Papillary Renal Carcinoma
  • Mouse Studies of VHL gene
  • VHL Gene Function
  • HIFα
  • Downstream effects of VHL mutation
  • Targeting VHL/HIF in Clear Cell RCC
  • TCGA Clear Cell Kidney Cancer
  • Intratumor Heterogeneity
  • Warburg effect in clear cell kidney cancer
  • Non-Clear Cell RCC
  • Locally Advanced Kidney Cancer
  • Hereditary Papillary Renal Carcinoma (HPRC)
  • Inherited Renal Carcinoma
  • Type 1 Papillary Renal Carcinoma
  • Penetrance of MET Mutation H1210R
  • MET Gene: Type 1 Papillary RCC
  • Location of the HPRC Gene
  • HPRC: Activating Mutations in the Tyrosine Kinase Domain of MET
  • Location of MET Mutations in the HPRC Patients
  • Targeting MET RCC Gene Pathway
  • Potential Small Molecule Target: MET Tyrosine Kinase Inhibition
  • Foretinib: Dual VEGFR and MET Inhibitor
  • MiT Kidney Cancer TFE3, TFEB, MITF
  • UOK124, Papillary Kidney Cancer
  • UOK124, UOK120, UOK 146 & TFE3 Kidney Cancer
  • Inherited Renal Carcinoma Birt-Hogg-Dubé (BHD)
  • Birt Hogg Dubé Cutaneous Manifestations
  • Kidney Tumors in BHD
  • BHD Renal Tumor Pathology
  • BHD Lung Cysts
  • Identification of the BHD Gene
  • Cutaneous Fibrofolliculomas
  • BHD Gene: Chromophobe RCC
  • BHD Gene Locus: Chromosome 17
  • BHD Protein Sequence
  • FLCN Mutation Spectrum
  • Therapeutic Approach: What Kind of Gene is FLCN?
  • BHD Gene Analysis in BHD-Associated RCC
  • Somatic mutations in renal tumors from BHD patients
  • UOK 257, BHD -/- RCC cell line Study
  • How Does the FLCN Gene Function?
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  • BHD Deletion Specifically in the Kidney
  • BHDf/d/KSPCre Mouse Kidney Study
  • Hereditary Leiomyomatosis Renal Cell Carcinoma (HLRCC)
  • HLRCC: Cutaneous Manifestations, Uterine Leiomyomas
  • HLRCC: Papillary Kidney Cancer Type 2
  • Orangophilic Nucleoli + Perinucleolar Halos
  • Fumarate Hydratase Gene: HLRCC
  • UOK-262 Study
  • Loss of a Krebs Cycle Enzyme Can Lead to Kidney Cancer
  • Impaired citric acid cycle and “Warburg effect”
  • HLRCC-Renal Cancer: Glucose-Dependent
  • PET Scan
  • HLRCC novel treatment approaches
  • Kidney Cancer: a Metabolic Disease

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  • Gastrointestinal stromal tumours
  • MPNST in NF1
  • FDG-PET as a diagnostic tool
  • Hotspots for recombination & NF1 microdeletion
  • SUZ12-loss
  • Cafe-au-lait (CAL) macules
  • Skeletal defects in NF1
  • Learning disabilities in NF1
  • Simvastatin treatment for cognitive deficits
  • Mosaicism for NF1 mutation
  • Diagnostic problems
  • SPRED1 mutations & molecular mechanism of Legius syndrome
  • The RAS pathway proteins & genetic syndromes (RASopathies)
Play '5. Congenital syndromes of pain and painlessness'
5. Congenital syndromes of pain and painlessness More info
Prof. Geoff Woods

TOPICS COVERED IN THIS TALK

  • What is pain?
  • How much pain is someone suffering?
  • What is the use of pain?
  • Pain pathways
  • Types of pain (Nociceptive, Inflammatory, Neuropathic, mixed)
  • Primary erythromelalgia
  • Mutations in SCN9A cause erythromelalgia
  • Voltage-gated ion channels
  • Paroxysmal extreme pain disorder (familial rectal pain)
  • Mutations in SCN9A cause PEPD
  • Congenital insensitivity to pain
  • SCN9A gene map
  • Electrical activity of wild type versus mutant constructs
  • Low-copy number vector = pcDNA3JC
  • Exon 6 splice variants
  • Neuropathies HSANs
  • Rita Levi Montalcini
  • TRKA signalling
  • Hereditary autonomic and sensory neuropathy type 4 (HSAN4)
  • HSAN5
  • NGFB
  • Familial dysautonomia
  • Treatment of pain
  • Mendelian disorders of pain
CANCER GENETICS
Play '6. Inherited predisposition to breast cancer'
6. Inherited predisposition to breast cancer More info
Prof. Diana Eccles

TOPICS COVERED IN THIS TALK

  • Breast cancer incidence around the world
  • Roles of inherited susceptibility and environment in cancer
  • High and low risk inherited susceptibility genes
  • The BRCA1 and BRCA2 susceptibility genes
  • The rare high risk gene TP53
  • Genetic testing: current uses and future potential
Play '7. PTEN Hamartoma-Tumour Syndrome: a model for the practice of clinical cancer genetics'
7. PTEN Hamartoma-Tumour Syndrome: a model for the practice of clinical cancer genetics More info
Prof. Charis Eng

TOPICS COVERED IN THIS TALK

  • PTEN Hamaratoma Tumour Syndrome: A Model for the Practice of Clinical Cancer Genetics
  • Clinical cancer genetics
  • Evaluating and managing families with inherited cancer syndromes
  • Recognition of clinical signs of heritable cancer
  • PTEN hamartoma tumor syndrome as paradigm
  • Recognition
  • Gene-specific medical management
Play '8. NF2 & Gorlins'
8. NF2 & Gorlins More info
Prof. D. Gareth R. Evans

TOPICS COVERED IN THIS TALK

  • NF2
  • An autosomal dominant inherited tumours predisposition syndrome
  • Bilateral vestibular schwannomas
  • Schwannomas of other cranial and spinal nerve routes
  • Meningiomas-Ependymomas affected mainly the upper spine
  • Cataracts
  • Mutations in the NF2 gene Gorlin syndrome
  • An autosomal dominant inherited tumours predisposition syndrome
  • Multiple BCCs
  • Jaw keratocysts
  • Medulloblastoma
  • Mutations in the PTCH gene
Now Playing
9. The genetic basis of kidney cancer
Dr. W. Marston Linehan
THERAPY
Play '10. Mismatch repair deficient cancers diagnosis, treatment and prevention'
10. Mismatch repair deficient cancers diagnosis, treatment and prevention More info
Prof. Sir John Burn

TOPICS COVERED IN THIS TALK

  • Lynch syndrome (underlying single gene defect)
  • Microsatellites
  • Important genes containing repeat sequences
  • MSI testing (5 marker panel)
  • Mismatch repair (MMR)
  • The genomic pathogenesis of colorectal cancer (CRC)
  • EGFR and BRAF mutant inhibition
  • BRAF colon cancer project
  • Methotrexate & MMR deficient tumours
  • Africans & bowel cancer (Dennis Burkitt)
  • Cancer prevention program (CaPP)
  • NSAIDs and reduced colorectal cancer risk
  • Aspirin effect on polyps in FAP and colorectal adenoma
  • The prevention paradox
  • CaPP2 (Colorectal & Lynch syndrome cancers)
  • Meta-analysis of cancer deaths with aspirin treatment
  • CRCs in people on aspirin (mostly COX2 negative)
  • Individual response to aspirin in cancer prevention
  • History of salicylate as an essential nutrient
  • CaPP3 study
  • Peptides created by slippage in microsatellite coding
  • Antibodies as a possible biomarker for Lynch syndrome
  • The Micoryx vaccine

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