Current concepts and trends in cancer genetics Adam J. Dupuy, MS, Ph.D. Associate Professor Department of Anatomy and Cell Biology Holden Comprehensive Cancer Center Cancer Genes & Pathways Program, co-Leader Carver College of Medicine University of Iowa
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Current concepts and trends in cancer genetics · Current concepts and trends in cancer genetics Adam J. Dupuy, MS, Ph.D. Associate Professor Department of Anatomy and Cell Biology
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Current concepts and trends in cancer genetics
Adam J. Dupuy, MS, Ph.D.Associate ProfessorDepartment of Anatomy and Cell BiologyHolden Comprehensive Cancer CenterCancer Genes & Pathways Program, co-LeaderCarver College of MedicineUniversity of Iowa
Overview
• Review of basic concepts in cancer genetics
• Description of current genome sequencing methods
• Interpretation of cancer genomes
• Applications of cancer genome sequencing in cancer therapy
Cancer is caused by mutation (somatic or germ line)
• Only ~10% of cancer cases are caused by inherited cancer predisposition syndromes (p53, BRCA1/2, APC, NF1, etc.)
• Remaining cancer incidence is due to somatically acquired mutations
Mutation happens...
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C T
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~186DNA repair
proteins
> 50,000 DNA damaging events per
day in each cell
exposures to carcinogens
Somatic mutations accumulate in “normal”
tissue with age
image by ScienceNews.org
Health consequences of elevated mutation rate
Environmental exposures
Genetic defects
Lifestyle choices
DNAdamage
incomplete DNA repair
Cancer
Immune disorders
Accelerated aging
Neurological disorders
DNA repair
Mutation
Health consequences of elevated mutation rate
Environmental exposures
Genetic defects
Lifestyle choices
DNAdamage
incomplete DNA repair
Cancer
Immune disorders
Accelerated aging
Neurological disorders
Health consequences of elevated mutation rate
Environmental exposures
Genetic defects
Lifestyle choices
DNAdamage
incomplete DNA repair
Cancer
Immune disorders
Accelerated aging
Neurological disorders
The evolution of cancer
• How many mutations are found in an average tumor?
• Which gene mutations cause cancer?
• Can this information be used to improve treatment?
Multi-step model of cancertubular adenoma precursor villous adenoma precursor
Many mutations and time are required to produce a tumor
What are “cancer drivers”?
Tumor suppressor gene:
• A gene whose partial or complete inactivation, occurring in either the germ line or the genome of a somatic cell, leads to an increased likelihood of cancer development.
• Such a gene that is responsible for constraining cell proliferation.
• Description of current genome sequencing methods
• Interpretation of cancer genomes
• Applications of cancer genome sequencing in cancer therapy
Next-Generation DNA sequencing(Emulsion PCR method)
image take from: Goodwin S, McPherson JD, McCombie WR. Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet. 2016 May 17;17(6):333-51.
Next-Generation DNA sequencing(solid-phase amplification method)
image take from: Goodwin S, McPherson JD, McCombie WR. Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet. 2016 May 17;17(6):333-51.
Overview
• Review of basic concepts in cancer genetics
• Description of current genome sequencing methods
• Interpretation of cancer genomes
• Applications of cancer genome sequencing in cancer therapy