Term
| Range of mutation rates in different cancers |
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Definition
•Dependence on carcinogens
•Age dependence
•Most mutations are passengers |
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Term
| What are distinct mutational signatures? |
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Definition
–Age
–APOBEC family of cytidine deaminases
–mutagenic exposures
–defects in DNA maintenance
–hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types |
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Term
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Definition
| The CpG sites or CG sites are regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its length. |
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Term
| What mutation are most frequent in CpG islands and why? |
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Definition
| Mutations from C to T via methylation and deamination, because T is not detected by repair enzyme. From cytosine to uracil via deamination is recognizable. |
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Term
| How many mutation signatures does cancer posses? |
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Definition
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Term
| What is APOBEC signature? |
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Definition
•C > X mutations at TpC sites
•APOBECs are cytosine deaminases (i.e. C=>T) involved in viral defense and mRNA editing
•Some also edit DNA (hypermutation in IG locus)
•Recently been identified as genes that can induce mutations in cancers |
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Term
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Definition
| kataegis describes a pattern of localized hypermutation identified in some cancer genomes. |
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Term
| Main features of kataegis |
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Definition
•Local hypermutations
•APOBEC involvement
•Somatic hypermutations in B and T-Cells
•TpC context |
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Term
| PINGO:A driver gene is defined |
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Definition
| A gene for which driver mutations have been found |
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Term
| PINGO:A driver mutation is described as R445T for a particular gene X. What statements are correct? |
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Definition
This is a missense mutation
X is a protein-coding gene
This mutation changes an arginine to a threonin |
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Term
| PINGO:What is the definition of driver mutations in the context of cancer genomics? |
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Definition
| Mutations that provide a selective growth advantage for the cancer cells in which they occur |
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Term
| PINGO:Which statements regarding the identification of driver genes are correct? |
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Definition
+The power to detect driver genes increases with an increasing number of patients
+The power to detect driver genes increases if one distinguishes mutational patterns expected for oncogenes and tumor suppressor genes
+Driver genes listed in cancer genome papers are in most cases identified by a statistical enrichment of somatic mutations in patient samples of a particular cancer type |
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Term
| PINGO:Which factors are likely to increase the false positive rate of driver gene identification? |
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Definition
+Not considering differences in the mutation rate in different genomic regions
+Not considering that longer genes have more mutations
+Not considering that transcribed genes have a lower mutation rate |
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Term
| PINGO: Why CpG mutations are enriched? |
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Definition
+CpG mutations are enriched because the deamination of methylated cytosine could not be recognized by the repair machinery
+CpG mutations are enriched because the large fraction of CpGs are methylated
+CpG=>CpA mutations are enriched because deamination of methylated C on the other strand leads to a C->T change |
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