Term
| Outline the work flow of cancer genome sequencing |
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Definition
| 1)Biopsy,matched tissue collection and pathology 2)DNA/RNA extraction 3) Sequencing 4) Alignment to the reference genome 5)Analysis and genomic characterization 6)integration and interpretation 7)treatment plan |
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Term
| Outline the problems with cancer genome sequencing |
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Definition
| Sample purity (fraction of tumor cells >60%),Sample quality (amount),degraded DNA (formalin fixed samples), cancer heterogeneity (different clones),coverage |
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Term
| What types of mutation exist in cancer? |
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Definition
Single nucleotide variants
Chromosomal rearragmenets, amplifications
Small indels |
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Term
| What problems with cancer genome sequencing are linked to soma vs. germline or polymorphisms vs. rare? |
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Definition
–Matched normal control
–Exclude common SNPs using databases |
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Term
| What should we do to minimize false positive rate of mutation discovery in cancer sequencing? |
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Definition
–Matched normal control
–Exclude common SNPs using databases |
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Term
| What is better for cancer genome sequencing paired or single ends? |
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Definition
| Paired end sequencing provides important structural information |
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Term
| What coverage should we achieve for genome sequencing? |
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Definition
–30-60 coverage for whole genome
–100-150 fold for exomes |
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Term
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Definition
| A mutation that exists in the vast majority of the neoplastic cells within a tumor. |
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Term
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Definition
A gene that is expressed aberrantly in
cancers in a fashion that confers a selective growth advantage. |
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Term
| What is gatekeeper mutations? |
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Definition
| A gene that, when mutated, initiates tumorigenesis (RB,VHL) |
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Term
| What is human leukocyte antigen? |
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Definition
| A protein encoded by genes that determine an individual’s capacity to respond to specific antigens or reject transplants from other individuals |
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Term
| What is missence mutation? |
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Definition
| A single-nucleotide substitution that results in an amino acid substitution (e.g., histidine to arginine). |
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Term
| What is nonsence mutation? |
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Definition
| A single-nucleotide substitution (e.g., C to T) that results in the production of a stop codon |
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Term
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Definition
| A gene that, when activated by mutation, increases the selective growth advantage of the cell in which it resides |
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Term
| What is passenger mutation? |
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Definition
| A mutation that has no direct or indirect effect on the selective growth advantage of the cell in which it occurred. |
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Term
| Outline the most common mutations in cancer |
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Definition
| single-base substitutions, indels, amplification, deletion, translocation |
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Term
| PINGO: You sequence an autosomal gene by high-throughput sequencing from a cancer sample of a patient. You find that of 1000 reads covering a particular site ~20% carry a particular mutation changing a conserved arginine to a histidine. Which conclusions can be drawn: |
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Definition
-Since the frequency is significantly below 50% it is likely that this mutation is not present in the germline
-If the fraction of cancer cells in the sample is ~80% than this mutation is likely to be heterozygous in all cancer cells in the patient |
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Term
| PINGO: You sequence an exome of a cancer sample and a germline control, run a pipeline to identify single nucleotide variants specific to the cancer sample and are told that the sequencing error rate is 1 in a million bases. You identify in the ~30 Mbp of exome sequence 60 single nucleotide variants. What percentage of these variants do you expect to be really present in the cancer sample? |
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Definition
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