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HG_II_Lecture_4
Cancer Genomics 3
24
Biology
Graduate
07/11/2014

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Term
What are driver genes?
Definition
All genes that confer a growth advantage to tumor cells
Term
What are passengers genes?
Definition
Mutations in passengers genes are not conferring any growth advantage
Term
How could we overcome resistance of cancer cells to death?
Definition
Proapoptotic drugs, BH3 mimetics
Term
How could we overcome deregulating of cellular energetics in cancer cells?
Definition
Aerobic glycolisys inhibitors
Term
How could we overcome sustaining prolifirative signaling in cancer cells?
Definition
EGFR inhibitors
Term
How could we overcome evading of growth supressors in cancer cells?
Definition
Cyclin-dependent kinase inhibitors
Term
How could we overcome avoiding of immune response in cancer cells?
Definition
Immune activating anti-CTLA4 mAb
Term
How could we overcome enabling replication immortality in cancer cells?
Definition
Telomerase inhibitors
Term
How could we overcome tumor promoting inflamation in cancer cells?
Definition
Selective anti-inflamatory drugs
Term
How could we overcome active invasion and metastasis in cancer cells?
Definition
Inhibition of HGF
Term
How could we overcome inducing angiogenesis in cancer cells?
Definition
Inhibitors of VEGF signaling
Term
How could we overcome genome instability and mutations in cancer cells?
Definition
PARP inhibition
Term
What leads translocation of Bcr-Abl Genes to?
Definition
The translocation occurs between chromosomes 9 and 22, it rearrangement of genomic material creates a fusion gene call Bcr-Abl that produces a protein (tyrosine kinase) thought to promote the development of leukemia.Constitutively active oncogene
Term
What is ABL1?
Definition
ABL1 (Abelson murine leukemia viral oncogene homolog 1) is a cytoplasmic tyrosine kinase
Term
How bcr-abl can lead to cancer? How Gleevec works?
Definition
Bcr-abl binds ATP and transfers phosphate from ATP onto specific tyrosine residues of substrate proteins. And it's these substrate proteins that induce all the phenotypic abnormalities we see in CML. Gleevec blocks binding of ATP to Bcr-abl.
Term
PINGO: What does TCGA mean?
Definition
The cancer genomic atlas and an initiative of the American National Institute of Cancer (NCI)
Term
PINGO: main feature of TCGA
Definition
With over 900 Terabytes of data, it is currently the largest genomic project
Data does not only include genome sequences, but routinely also RNA-Seq and methylation data
The data is publicly available
Term
What are three main steps of Illumina sequencing?
Definition
Library preparation, cluster generation and sequencing
Term
Outline the steps of Ilumina sequencing
Definition
1) Destroy DNA with ultrusound 2) Exonuclease and polymerase to make ends blind 3) Add A and adapters 4) Extract fragments 200-500 bp long with gel 5) PCR with primers to adapters 6) Generate clusters on flow cell with brodge amp 7)Nick and get oosDNA 8) Fluorophores 9)
Term
Two sources of genome annotation are...
Definition
comparative and functional
Term
PINGO: What statements regarding the Philadelphia chromosome are correct?
Definition
It is a rare reciprocal translocation in chronic myelogenous leukemia (CML)+
+It is a reciprocal translocation leading to the Bcr-Abl fusion gene
It leads to the constitutive expression of the Bcr gene
+It carries the Bcr-Abl fusion, leading to the expression of a constitute active tyrosine kinase
Term
Which statements regarding the Illumina sequencing platform are correct?
Definition
It is currently the dominating platform for Next-Gen Sequencing
Term
Illuminas HiSeq X Ten machine
Definition
+was released in January 2014
+is able to sequence human genomes for 1000 Dollar (excluding analysis and overheads)
+ten machines can sequence more than 18000 human genomes per year
Term
What is the main reason to sequence the genome or exome of a normal tissue (germline control) in addition to the cancer sample from a patient?
Definition
Because it allows to distinguish mutations that occurred during the emergence of the cancer from germline mutations
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