Driver mutations and cancer

Oncogenes- genes Is mutated. As result it causes abbarent cell cycle progression, usually genes involved in positive cell cycle progression, cyclin D1, CdKs, if you see gene amplificaiton or mutation that results in cell proliferation Tumor suppressor genes - genes that hit brakes on cell cycle progression, p53, usually you see loss of funct or delection in cancer cells

driver - mutation that provides selective growth advantage (happen in oncogenes and tumor suppressors) Mutations that silence tumor suppressors Stops the cell from pressing on the break. Also if they happen on oncogenes, they would be gain of function mutation Passanger - mutation that does not provide selective growth advantage. Happen due to increase genomic instability, consequence of cancer

proto oncogene

sustaining proliferative signaling evating growth suppressors avoiding immune destruction enablin replicative immortality inducing vasulature genome instability and mutation resisting cell death deregulating cell metabolism

RSV - sous sarcoma virus, found in chickens the virus induced tumors Normally cells have Contact inhibition, cells stop dividing if it is surrounded if you infect normal cell with the RSV it will not longer have contact inhibition

Rous sarcoma virus Virus hijacks host machinery after its integrated into genome it adds its virus gene into host DNA src gene which helps with proliferation(usually there are only 2 copies in gene but it can add another) src is example of proto oncogene, its a non-receptor tyrosine kinase

oncogenes - mutated version of genes that make proteins, important to signal transduciton pathway(receptors, kinases, trans factors), leads to cell transformation proto oncogenes - normal, unmutated counterpart of oncogenes, usually gain of funct mutation ex src - When proto oncogene src is integrated into the host DNA then it becomes oncogene

The basement membrane is no longer present in invasive cancers The invasion through memb is what we call matastasis

Her2 is example of tyrosince kinarse Part of epidermal growht factor family Stimulates growth, prolifereation when it is active Myc stimulates cyclin d1 expression Cyclin d1 is also protooncogene

through inheritance of retinoblastoma- binds to** E2F** and functions as a repressor to repress cyclin E,A is a recessive loss of function scientist found that those with history of retinoblastoma are more likely to get it in both eyes. because they start with mutation in at least 1 copy of gene.

P21 - cyclin dependant kinase inhibitor (CDK), stops cell cycle if DNA is damaged, related to p53 p53 - apoptosis transcription factor retinoblastoma gene -inhibits too much cell growth

Unlike many other tumour suppressors, p53 often involves missense mutations that lead to loss of function.

onco - Are dominant. * gene amplification, in some cases activating GOF missense mutations tumor suppressor - Are recessive. * Arise by focal deletions or nonsense, frameshift, and splice-site mutations. In some cases (e.g., p53) missense mutations.

the cells within a tumor do not share the same protein receptors, diff parts of tumor will respond to diff treatments ex. estrogen, progesterone and Her2 receptors. in breast cancer. difficult to treat cells that do not have any of their receptors

tumour suppressors require both copies of a gene to be inactivated to drive cancer

targeted panel - only look at genes that are known related to disease whole exome - seq only exonic regions of protein coding genes, only look at coding region, mid speed whole genome - all genome is seq, is expensive

It is used to detect and locate specific DNA sequences on chromosomes, helping identify genetic aberrations. the genes glow

Nucleosome - single unit of DNA around a core of Histones Cromatin - severale repeating nucleosome units euchromatin - if transcriptionally acive Heterochromatin - silent in transcription

A change in gene expression that occurs without a change in the underlying DNA sequence. has histone, DNA and chromatin remodelling

acetylation - histone acetylases(HATs) adds acetyl group, makes DNA neutral, can be read, activates gene, deacetylation - Histone deacetylases (HDACs) silencces gene, takes away acetyl group, DNA is more tightly wrapped around histone bc hist is pos and DNA is now neg methylation

Methylation of cytosine nucl next to guanine nucl (CpG dinucleotide) CpG often found in gene regulatory regions DNA methly transfereases (DMNTs)- add methyl groups methyl group to cytosine nucleotide, inactivates transcriptionjjd then Readers (ex MeCP2) bind to the meCpG to recruit co repressors like HDACs to go to hetochromatin formation

through multi protein complexes, in ATP activated manner ex SWI/SNF (ARID1A is part of this) complexes, the complexes can have diff parts which dictate function 1. slide nucleosome out of way 2. evict nucleosome 3. excahnge nucleosome

Do not have expression for receptors of ER, PR or Her2