Cancer 1 redo Flashcards
What is Cancer?
- Cancer is a term used for a group of diseases in which cells divide in an abnormal manor.- Subsequently these cells are able to invade other tissues
There are more than […] types of cancer.
- There are more than 100 different types of cancer.
Most cancers are named for the…
…organ or type of cell in which they start
Further cancers can be grouped depending on the …
…type of tissue they originate from
Define carcinoma
cancer that begins in the skin or in tissues that line or cover internal organs.
Define sarcoma
cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.
Define leukemia
cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood.
Define Lymphoma and myeloma
cancers that begin in the cells of the immune system.
Define Central nervous system cancers
cancers that begin in the tissues of the brain and spinal cord.
What are the different Hypotheses of the Origin of Neoplasia?
- Viral Oncogene Hypothesis 2. Oncogenes and Tumor Suppressor Genes 3. Epigenetic Hypothesis 4. Failure of Immune Surveillance
Define malignant
if tumor invades surrounding tissue (cancerous)
Define Metastatic?
If individual cells break away and start a new tumor elsewhere. (cancerous)
Define benign
if tumor has no effect on surrounding tissue (non cancerous)
Proto-oncogenes have…
…regulatory functions in the development & growth of the cell
Changes in expression or function of proto-oncogenes lead to…
… a cell becoming cancerous
Proto-oncogenes are examples of…
…growth signaling components
When a proto-oncogene changes its expression or function it is termed…
…an oncogene
What happens when a proto-oncogene turns into a oncogene?
The cell becomes cancerous
Viral oncogenes are…
…homologues of cellular control genes that disrupt cell cycle control
There are three main mechanisms that …
…may lead to a cell losing it’s ability to regulate its cell cycle
What are the three main mechanisms that may lead to a cell losing it’s ability to regulate its cell cycle?
- ‘Hijacking’ of the cell cycle * e.g. by viral pathogens 2. Altered protein function * e.g. Mutation of the DNA coding region 3. Inappropriate activation/repression of genes * e.g. Mutation of the DNA control regions of a gene * e.g. Loss of epigenetic control mechanisms
The first oncogene product with an explicit function was the…
…v-SIS protein
Whats the v-SIS protein?
a modified form of platelet-derived growth factor (PDGF)
Infection of cells with simian sarcoma virus, which harbours v-SIS, results in…
…production of functional PDGF- This autocrine stimulation generates a chronic growth stimulus for PDGF-responsive cells
Organism infections assoicated wit human cancer?
- Hepatitis B & C Virus * Human Papilloma Virus * Epstein-Barr Virus * Human T-Cell Lymphotropic Virus * HIV & Human Herpesvirus 8 * Heliobacter pylori * Schistosomes * Liver fluke
Cancerous infections associated with human cancer?
- Liver Cancer * Cervical Cancer * Burkitt’s Lymphoma * Adult T-cell Leukemia * Kaposi’s Sarcoma * Gastric cancer * Bladder cancer * Cholangiosarcomas
Receptor oncogenes are activated in human cancers by…
…gene amplification (which leads to over-expression), rearrangements, and point mutations
Both N- and C-terminal deletions can…
…partly activate the transforming potential of receptor tyrosine kinases- As found in a subset of non-small-cell lung cancer (NSCLC)
What is NSCLC?
non-small-cell lung cancer
Activating mutations in the TK domain of EGFR are limited to…
…the first four exons, and show a remarkable structural diversity, including point mutations, deletions, and insertions.
Whats EGFR?
Epidermal growth factor
Different forms of mutations are found at differing rates in…
…NSCLC
L858R is a…
…point mutation in exon 21
The EGFR mutations result in…
…tyrosine kinase activity even when no growth factor is bound- (the cell is continually being told to grow and reproduce)
What happens in the Transduction pathway?
- Signal passes through cell* Response - Activation/deactivation of a process
RAS is a…
…signal transduction protein of the G-protein family
Activations of RAS G proteins are the most common…
… dominant mutations in human cancer
Point mutations that activate RAS genes are clustered in …
…the regions encoding amino acids 12, 13, and 59 to 61
Point mutations that activate RAS act by…
…interfering with the guanine triphosphate (GTP) hydrolysis step of the RAS-GNP cycle
RAS functions analogously to other G proteins that cycle between …
… inactive guanine diphosphate (GDP)-bound states and active GTPbound forms
The GTP-bound forms activate downstream signaling proteins until …
…GTP hydrolysis which is mediated by the intrinsic activity of RAS returns the system to the basal state
Transforming mutants of RAS are…
…resistant to the GTPase
Transcription factors control…
…gene expression
Transcription factors can:
- They can induce gene expression e.g. myc * They can repress gene expression
Transcription factors are frequently controlled by…
… hormones (e.g. growth factors) via signal transduction pathways
There are four basic types of effects of transcription factors which are…?
- Progression from G1 to S phase in the cell cycle * Genome stability * Apoptosis * Cellular maturation
Inhibitors of cell cycle progression?
tumour suppressors
The oncogenic mechanism of c-MYC is not fully understood, but it…
…regulates many genes
inappropriately regulated expression of c-MYC, rather than mutations in the protein, contributes to …
…tumorigenesis
c-MYC activation by…
…chromosomal translocation in Burkitt’s lymphoma
c-MYC tends to be activated by…
…mechanisms 1 & 2
What is mechanism 1?
Translocation or transposition: gene moved to new locus under new controls.
Whats mechanism 2?
Gene amplification: multiple copies of the gene.
Positive Regulators of the Cell Cycle?
- Cyclins and CDKs are the core apparatus of cell cycle progression
Methylated CpGs are associated with …
… silenced DNA, e.g. Transposons, inactive X chromosome, imprinted genes
How many major classes of methylases in mammalian systems?
2 major classes
WHat are methylases necessary for?
for the survival and proper development
WHat is Genomic imprinting?
- Gene silencing inherited from parents - Alleles silenced will depend on parental origin
Genes get turned on because they become…
…demethylated
What is hypomethylation a theorised major cause of?
Theorised major cause of cancer
Hypomethylation results from…
…the lack of a methylating agent
What were the conclusions of the study titled “Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences”?
“These analyses were deployed to compare chromosome-wide DNA methylation patterns in normal and malignant prostate cells, revealing significant enrichment of DNA methylation and hypermethylation of gene-proximal genomic regions” “Several of these newly identified cancer hypermethylated regions were highly effective as DNA methylation based biomarkers capable of sensitively and specifically distinguishing malignant from normal prostate tissues and cell lines.”
the cell is constantly checking that…
…division is appropriate and is progressing correctly
What are the phases of the The Mitotic Cell cycle - control?
1) G1 Interphase2) S-Phase3) G2 Interphase4) M-Phase
When the check points of the cell cycle fail to function …
…the cell can become cancerous = uncontrolled cell division
Gene products that manage these checks are often called…
…Tumour Suppressors because they can suppress tumour formation
Tumour Suppressor Rb binds to…
…transcription factor E2F and prevents gene expression of proteins needed to go to S phase e.g. c-MYC
Tumour Suppressor P53 halts…
…progression when the DNA is damaged
Why does tumor suppressor P53 halt progression when the dna is damaged?
- to give cell time to repair or to triggers apoptosis of damaged cell * If damaged (mutated) cell moves to S phase then it may replicate * Most frequent mutated gene in human cancers
The p53 gene is called the…
…“guardian angel of the genome”
BCL-2 is an…
…Apoptosis Regulator
BCL-2 over-expression can…
… block apoptosis that is induced by any of a number of signals, including radiation, chemotherapeutic agents, growth factor withdrawal, steroids, and heat shock
BCL-2 gene encodes…
…an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes.
ROle of BCL-2 gene in Follicular lymphomas?
puts the BCL-2 gene under transcriptional control of the Ig heavy chain gene, resulting in BCL-2 over-expression
What is Ataxia-telangiectasia (AT)?
recessive disorder that causes a number of abnormalities, including predisposition to lymphoid neoplasms
Ataxia-telangiectasia is associated with…
…defects in DNA repair (AT is a DNA repair checkpoint)
AT is a …
…DNA repair checkpoint
ATM may be involved in a…
…significant number of cancers
Mutations that impair the ability of cells to recover from DNA damage can…
…enhance the spontaneous mutation rate and lead to cancer
Analysis of families carrying the trait suggests that ATM heterozygotes are…
…at a somewhat greater risk for cancer development, notably breast cancer
The DNA mismatch repair system is responsible for a …
…major hereditary form of colon cancer, hereditary non polyposis colorectal cancer (HNPCC)
What is described as type I (1)?
GROWTH FACTORS
What is described as type II (2)?
Growth Factor Receptors
What is described as type III (3)?
Signal Transducers
What is described as type IV (4)?
Transcription Factors
What is described as type V (5)?
Cell cycle -control - Tumour Suppressors
What is described as Type VI (6)?
Apoptosis Regulators
What is described as Type VII (7)?
DNA-repair enzymes
