PBL 6 by Mohammad Darvish https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5 Cancer cell genes: drivers and passengers en-us 2021-12-08 23:13:58 UTC 2023-02-14 01:59:26 UTC hello@padlet.com What are they? mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936960580 All genes whose alteration contributes to the causation or evolution of cancer by driving tumorigenesis  
Oncogenes & tumour suppressor genes]]> 2021-12-08 23:15:10 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936960580 What is their role in cancer? mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936960708 2021-12-08 23:15:17 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936960708 What are they? mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936961723 2021-12-08 23:16:36 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936961723 Proto-oncogene to oncogene mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936962163 Mutation in coding sequence: hyperactive protein

Mutation in regulatory: normal protein overproduced

Gene amplification: normal protein overproduced

Chromosome rearrangement: nearby regulatory DNA sequence causes normal protein to be overproduced OR fusion to actively transcribe gene produces hyperactive fusion protein



Example Myc:
overproduce of normal protein (regulatory mutation)

Burkitt's lymphoma:
translocation - sequence of one chromosome is cut, placed onto the other -> difference in length
B-lymphocytes
Myc gene https://youtu.be/BADXO2Tezhk

]]> 2021-12-08 23:17:05 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936962163 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936962621 Binding of EGF results in intracellular signalling - mutation of the extracellular domain can result in receptors triggering the signal without EGF]]> 2021-12-08 23:17:41 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936962621 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936962719 Two different chromosomes containing different genes get translocated (parts of both fuse together)
this gene undergoes further transcription and translation -> the protein made contains genetic information from both (can become hyperactive)]]> 2021-12-08 23:17:48 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936962719 Tumour suppressor gene: loss of function mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936963183 (loss of function mutation: destroy cellular activity | generally recessive) – corresponding normal form: tumour suppressor gene ]]> 2021-12-08 23:18:20 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936963183 Oncogene: gain of function mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936963451 (gain of function mutation: protein hyperactivity | only one gene copy needs to be mutated) – corresponding normal form: proto-oncogene 
Myc protein: act in the nucleus to stimulate cell growth and division – contribute to cancer by being overproduced in its normal form

]]> 2021-12-08 23:18:39 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936963451 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936963726 Retinoblastoma – loss of function mutation present in one copy of Rb in every somatic cell

Hereditary: inherited one Rb gene - other gene mutated → retinoblastoma
Nonhereditary: inherit two good genes: both genes mutate → retinoblastoma 
]]> 2021-12-08 23:18:59 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936963726 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936963822 2021-12-08 23:19:06 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936963822 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936965088 2021-12-08 23:20:30 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936965088 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936965822 Karyotype contains 48 instead of normal 46 -> can cause cancer]]> 2021-12-08 23:21:21 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936965822 How does the process work? mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936966183 Cell starts off with one mutation -> gains more mutation each cell cycle (cells around will also have mutations) -> malignant
Loss/gain of function: loss of contact inhibition and uncontrollable replication


(refer to mutations and genetic instability]]> 2021-12-08 23:21:46 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936966183 Difference between genetic and epigenetic mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936966447 genetic looks at change in DNA sequence
epigenetic look at other heritable changes (external)]]> 2021-12-08 23:22:05 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936966447 Drivers mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936966785 Mutations that provide selective growth advantage]]> 2021-12-08 23:22:30 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936966785 Passengers mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936967040 Neutral - play no role in cancer development]]> 2021-12-08 23:22:47 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936967040 How to distinguish them? mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936967178 Frequency of occurrence - 
Drivers are influential thus happen only in a subset of the population
passengers are random]]> 2021-12-08 23:22:56 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936967178 Genetic modifications mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936968086 Retinoblastoma – using chromosomal deletion, Rb gene was cloned and sequenced. Deletion or loss of function mutation present in one copy of Rb in every somatic cell → retinoblastoma (very rarely both copies can be destroyed, this is non-hereditary retinoblastoma)
Rb genes are also missing in several other types of cancer: carcinomas of lung, breast, bladder
Rb genes encode Rb protein: universal regulator of cell cycle -> when this loss of function occurs, Rb protein is no longer produced

]]> 2021-12-08 23:24:01 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936968086 Epigenetic modifications mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936968183 DNA hypermethylation: adds methyl group on the DNA -> silences the gene]]> 2021-12-08 23:24:09 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936968183 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936968910 2021-12-08 23:24:56 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936968910 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936969559 Apc is a tumour suppressor gene: changes that lead to genetic and epigenetic instability are likely to arise early in tumour progression
 K-Ras gene (monomeric GTPase) occur later, controls cell growth and cell death → no more conversion to GDP
p53 function allows cancer cells to endure stress and to avoid apoptosis and cell-cycle arrest → loss of p53 is related to the heightened activation ]]> 2021-12-08 23:25:42 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936969559 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936971402 2021-12-08 23:27:43 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936971402 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936971568 2021-12-08 23:27:54 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1936971568 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937942468 Takes a long time for an individual clone of cells to accumulate large number of mutations -> genetic instability -> interferes with accurate replication and maintenance of the genome -> increases the mutation rate
Changes of karyotype ]]> 2021-12-09 11:25:34 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937942468 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937954102 Benign tumour: does not have ability to invade surrounding tissue

Malignant tumour: ability to invade surrounding tissue, often break lose from primary tumour and enter bloodstream/lymphatic vessels (metastases)

]]> 2021-12-09 11:34:09 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937954102 p53 tumour suppressor mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937962233 p53: activated only in certain occasions - concentration of p53 only when hyperproliferative signals/DNA damage/telomere shortening/hypoxia occurs → p53 tell the cell to follow cell-cycle arrest/senescence/apoptosis

Mutation: weakens the ability of p53 → cannot combine to perform cell-cycle arrest/etc (example of loss of function)]]> 2021-12-09 11:40:05 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937962233 mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937966838 Ras: family of proto-oncogenes

Monomeric GTPases that help transmit signals from cell-surface receptors to cell interior

Ras oncogenes contain point mutations that create hyperactive Ras protein that cannot shut off by hydrolysing its bound GTP to GDP

]]> 2021-12-09 11:43:23 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937966838 Retrovirus as vector mohammaddarvisheuc https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937985625 When it infects a cell its RNA genome is copied into DNA by reverse transcription and the DNA is inserted into the host genome (persists and is inherited by subsequent generations of cells)

Src – normal c-Src -> oncogene v-Src

]]> 2021-12-09 11:57:10 UTC https://padlet.com/mohammaddarvisheuc/74pw5pzes1bccpn5/wish/1937985625