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HG_II_Lecture_3
Cancer genomics 2
27
Biology
Graduate
07/10/2014

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Term
What are the differences between somatic and germline mutation?
Definition
Germline mutations: present in egg or sperm, are heritable,cause cancer family syndrome, all cells affected in offspring
Somatic: occur in nongermline tissues, are nonheritable
Term
What role in cancer does epigenetics play?
Definition
Most (all?) epigenetic memory is erased across generations => no Lamarckian inheritance across generations ->germline epigenetic changes play “no” role in cancer
Transcriptional state is inherited within an organism via DNA methylation, histone mdifications, inheritance of trnascription factors->epigenetic changes play a large role in cancer
Term
What virus causes sarcoma in chicken?
Definition
Rous sarcoma virus
Term
What are the main features of Ras?
Definition
•PROTO-ONCOGENE
•Short for „Rat sarcoma“
•A small GTPase
•3 Ras genes in humans (HRAS, KRAS, and NRAS)
•mutations that permanently activate Ras are found in 20% to 25% of all human tumors and up to 90% in certain types of cancer
•Gain-of-function mutation
Term
What is HER-2/neu?
Definition
•PROTO-ONCOGENE
HER-2/neu encodes for a cell surface receptor that can stimulate cell division. The HER-2/neu gene is amplified in up to 30% of human breast cancers.
Term
What is Myc?
Definition
•PROTO-ONCOGENE
The Myc protein is a transcription factor and controls expression of several genes
Term
What is hTERT?
Definition
•PROTO-ONCOGENE
hTERT codes for an enzyme (telomerase) that maintains chromosome ends.
Term
What types of mutations should you expect for oncogenes?
Definition
activating mutations – gain-of function - dominant
Term
What could mutations in proto-oncogenes lead to?
Definition
1) hyperactive protein made in normal amount
2) normal protein which is overproduced
3) nearby regulatory DNA sequence causes normal protein to be overproduced
4) fusion to actively transcrabed gene produced hyperactive fusion protein
Term
What are the two major types of mutations, leading to cancer?
Definition
Gain of function
Loss of function
Term
What is Myc gene doing?
Definition
Myc (c-Myc) is a regulator gene that codes for a transcription factor.

A mutated version of Myc is found in many cancers, which causes Myc to be constitutively (persistently) expressed.
Term
How mutation in Myc can lead to Burkitt's Lymphoma?
Definition
A common human translocation involving Myc is t(8;14), which is critical to the development of most cases of Burkitt's Lymphoma.
Term
What types of mutations should you expect for tumor suppressor genes?
Definition
Loss of function
Genetically recessive
Term
Genetic deficiencies in tumorogenesis
Definition
Genetic differences are present both in sporadic and congenital cancer
The affected genes are called tumor suppressors
Typically, both copies are defected
Deficiency are genetically inherited
Term
When is tumor suppressor genes are activated during the cell cycle?
Definition
In normal cells, tumor suppressor genes act as braking signals during G1 to stop or slow the cell cycle before S phase.
Term
How tumor suppressor gene participates in cancer?
Definition
Both copies of a tumor suppressor gene must be lost or mutated for cancer to occur. A person who carries a germline mutation in a tumor suppressor gene has only one functional copy of the gene in all cells. For this person, loss or mutation of the second copy of the gene in any of these cells can lead to cancer.
Term
Two-Hit Hypothesis
Definition
If first hit is a germline mutation, second somatic mutation more likely to enable cancer
Term
What are hallmarks of cancer?
Definition
Evading apoptosis,
Self-sufficiency in growth signals
Insensitivity to anti-growth signal
Tissue invasion and metastasis
Limitless recitative ability
Sustained angiogenesis
Term
What are additional hallmarks of cancer?
Definition
Deregulated metabolism
Unstable DNA
Inflammation
Evading the immune system
Term
About how many functionally relevant mutations one considers as a minimum to transform a normal cell to a cancer cell?
Definition
6
Term
Examples of tumor supressor genes
Definition
P53 (gene TP53), RB1, BRCA1
Term
Name types of mutations needed to shut down the gene
Definition
Deletion or point mutation in coding sequence, regulatory mutations, gene amplification, chromosome rearrengment
Term
MAPK pathway
Definition
The pathway includes many proteins, including MAPK, which communicate by adding phosphate groups to a neighboring protein, which acts as an "on" or "off" switch. Also known as the Ras-Raf-MEK-ERK pathway.
Term
PINGO: You suspect that your gene of interest could be a tumor suppressor gene. Which types of mutations would be the most promising to screen for in a panel of cancer samples?
Definition
+Chromosomal deletions affecting the gene
+Mutations disrupting the open reading frame
+Epigenetic changes silencing the gene
Term
PINGO: About how many functionally relevant mutations one considers as a minimum to transform a normal cell to a cancer cell?
Definition
6
Term
PINGO:What statements are true regarding the Hallmarks of Cancer?
Definition
+It is the title of a review written by Hanahan and Weinberg in 2000
It is a list of genes that are often mutated in different cancers
+It is an attempt to categorize the functional capabilities that have been acquired by most cancers
Epigenetic change is one of the six hallmarks of cancer
+Limitless replicative potential and sustained angiogenesis are two of the six hallmarks of cancer
Term
PINGO: In 2011 Hanahan and Weinberg added four features to the classical hallmarks of cancer. Which is NOT one of them?
Definition
Drug resistance
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