Biology 3594A Study Guide - Final Guide: Temozolomide, Somatic Hypermutation, Mutagen
13 May 2018
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Lecture 15 Flashcards
Front (Term)
Back (Definition)
How they cluster the cancers and
mutations
Based on similarity of mutation in a particular context
- contexts are based on nt patterns
Mutation load/burden
aggregate number of mutations there
Clusters 1-3 vs. Clusters 4-8
Clusters 1-3 are replication-repair deficiency
Clusters 4-8 are non-replicationrepair deficiency (known
mutagen signatures)
Variant allele fraction
When doing NGS with read-depth analysis, VAF is how many
reads have the mutation in it
- reveals evolutionary dynamics in tumors, adds time
dimension to mutation analysis
- larger variant allele fraction (higher number of reads with
mutation) = earlier mutational event
- more time for mutations to accumulate??
- Smaller variant allele fraction indicates recent mutational
event
Different clusters have different evolution dynamics and
timing of hypermutation
The relationship between survivorship
and mutation burden
Clusters with lower variant allele fraction (2 and 3 vs. 1) have
better lower mutation burden and better patient survival
- mutations occurred later
(although survivorship is not always necessarily associated
with mutation burden?)
Mutational context 5'NNN3'
Middle N is the mutation
There are 96 different contexts
When you analyze the contexts as single trinucleotides you
can come up with over 30 cancer signatures
- respond to these differently treatment-wise
- clusters are based on these signatures
TMZ
Temozolomide
- chemotherapy, alkylating agent
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Based on similarity of mutation in a particular context. Clusters 4-8 are non-replicationrepair deficiency (known mutagen signatures) When doing ngs with read-depth analysis, vaf is how many reads have the mutation in it. Reveals evolutionary dynamics in tumors, adds time dimension to mutation analysis. Larger variant allele fraction (higher number of reads with mutation) = earlier mutational event. Smaller variant allele fraction indicates recent mutational event. Different clusters have different evolution dynamics and timing of hypermutation. Clusters with lower variant allele fraction (2 and 3 vs. 1) have better lower mutation burden and better patient survival. Mutations occurred later (although survivorship is not always necessarily associated with mutation burden?) When you analyze the contexts as single trinucleotides you can come up with over 30 cancer signatures. Tumours can have different cell populations within them that are different in size depending on when the mutation arose. The proportion of reads of a mutation can determine its abundance and when it occurred.
