Molecular basis of cancer Flashcards
define cancer
a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body
what two ways can stored information in the cell of a metazoan be affected to create cancer?
altered/currupted OR misused
Cancers are classified according to what three criteria?
- tissue of origin
- level of malignancy
- genetics
When the tissue of origin is epithelial, what is the name of the cancer?
& what percentage are they
Carcinoma
>80%
When the tissue of origin is mesenchymal tissue, what is the cancer called?
& what percentage are they
Sarcomas
~1%
When the tissue of origin is Hematopoetic tissue, what is the cancer called?
& what is the percentage they make
Lymphoma/ Leukemia
~10%
When the tissue of origin is Neuroectoderm, what is the cancer called?
& what percentage does it make up
Blastoma/ Melanoma
~5%
wht are the two parts of TMN staging?
breifly describe each
Staging = characteristics of a tumour
Grading = characteristics of tumour cells
What are levels of malignancy?
Mild hyperplasia
Advanced hyperplasia
Carcinoma in situ
Invasive carcinoma
Metastatic carcinoma
What three ways can cancer come about?
genetic & non genetic
Sporadic: no family history
Familial: mutation is unknown
Hereditary: mutation is known
What percentage of cancers are hereditary?
5-10%
what are the four stages in classification of the tissue of origin of breast cancer?
breifly describe advance of cancer in the milk duct
Mildly hyperplastic tissue:
More advanced hyperplasia: Lumen is visible but small, cancer cells contained
Ductal cacinoma in situ: No lumen, bleeding, no spread yet
Invasive ductal carcinoma: basement membrane broken, detachment of cells from main lump, invasding surrounding fat tissues
What are the 6 hallmarks of cancer?
- self sufficiency in growth signals
- insensitivty to antigrowth signals
- sustained angiogenesis
- evading apoptosis
- limitless replicative potential
- tissue invasion and metastasis
What is considered the ultimate hallmark of cancer?
And why?
Almost all the other hallmarks of cancer you see in other diseases, the only real hallmark is metastasis
Why is cancer a disease of clonal selection?
when a cell mutates, it can give it a survival advantage and so are selected for based on the selction pressure and clonally expand until the next mutation arrives to confer another advantage and then these cells are clonally expanded. this continues multiple times
What is an Oncogene?
How does it cause cancer?
A gene that has the potential to cause cancer
Mutation or overexpression of protooncogenes
what are the three ways of oncogene activtion?
Give 2 examples for each
- Activating mutations (eg Ras, CDK4)
- Gene amplifications (eg Myc, MDM2, Her2)
- Translocations (eg Myc/IgH)
What is MDM2?
An important negative regulator of the p53 tumour suppressor gene
Mouse double minute 2
Breifly how does Ras cause cancer
in terms of oncogene mutation
Mutation activating oncogene
Ras is a bottleneck for survival signals
Describe the activation of the Ras gene
Inactive Ras is bound by GDP
Upstream stimulatory signal and Ras activation is triggered by GEF (unbinding GDP)
Downstream signalling brings GTP to bind to Ras - it is now active
Often a blockage caused by an oncogenic mutation at this point prevents Ras inactivation
GTP hydrolysis and Ras inactivation is induced by GAP
What are the three Ras genes?
K-Ras
H-Ras
N-Ras
On different chromosomes, function similarly but differ in expression
Breifly how does EGRF2 (HER2) cause cancer
in terms of oncogene activation
Oncogene activation through amplification
How does HER2 (EGRF2) work?
And what happens when the oncogene is activated?
In a normal cell - cross phosphoyrylation (by the tyrosine kinase domasin) after ligand binding - ligand dependent binding
In a cancer cell– ligand independent firing (via mutation affecting structure or overexpression)
Patients with breast cancer live long if the Her2 gene is not ________
amplified