Gene Amplification Flashcards
What are the main steps in illumina NGS?
Library preparation
Clonal amplification
Sequence
Analysis.
What has the TCGA project showed us?
Molecular basis of cancer
Tumour subtypes
Therapeutic targets
(Whole exome sequencing)
What are the different types of driver mutations and how do they differ to passenger?
What is significant about cancer drivers?
Driver confer selective advantage to tumour.
Inactivating - loss of function
Activating - gain of function.
Passenger - mutations with no effect on neoplastic process.
They are cancer specific.
How do solid tumours and liquid tumours differ in terms of mutations?
Paediatric and liquid - stable but associated with chromosomal instability.
Solid - 1-10 mutations per tumour in CODING portions.
What are the classes of driver rearrangements and what type of sequencing can they be revealed by?
Whole genome sequencing.
Fusion transcripts
Oncogene amplification
TS deletion.
How is the myc oncogene altered?
V-Myc = avian myelocytomatosis viral oncogene homolog.
TF
Mutated in malignant melanoma
Hotspots for substitutions in Myc-N region.
What are the 2 patterns that predict occurrence of tumour relapse?
Dominant clone in primary tumour gained mutations and evolved –> relapse clone.
Minor subclone survives, gains mutations and expands at relapse
What are the applications of; whole exome, whole genome and subclonal mutation identification?
Catalogue of cancer genes, cancer mutations and rebuilding of tumour evolution.
What is another class of driver mutations?
mutations conferring cancer therapy resistance and found in recurrences. Limited growth advantage in absence of treatment - some may be passenger mutations in minor subclones pre treatment and then selective environment changed by therapy and passenger becomes driver.
