2.2 bio quiz soon
What is chromothripsis?
"chromosome shattering" can occur and and it is much more frequent than originally thought. Occurs in >50% in several cancer types (soft-tissue).
diploid
(genetics) an organism or cell having two sets of chromosomes or twice the haploid number
What is Oncogenic signature?
(no definition given in slides, this was the best i could find ): ) A set of genes that show a specific pattern of up- or down-regulation when a given pathway associated with oncogenesis is activated.
Mary-Claire King did what?
-1st to show breast cancer can be inherited. 1990 identified gene associated with increased risk breast cancer: BRCA1 on chromosome 17. -Pioneered use of DNA sequencing for human rights investigations. Kidnapped children in Argentina. -2020: Leading team to study Schizophrenia in Africa. -Advocate that every woman older than 30 should be offered testing for BRCA1 & BRCA2. -Developed a rapid screening test: BROCA -2015 BROCA - Cancer Risk Panel for breast & ovarian ~60 genes suspected hereditary cancer predisposition BROCA used throughout the world. Did not patent -Mary-Claire King: 1990 identified gene associated with increased risk breast cancer: BRCA1 on chromosome 17. -Myriad Genetics founded in 1994 pursued hunt for sequence. Published sequence of BRCA1 & filed a US patent. Published sequence of BRCA2 in 1995 & filed patent. -1996: Myriad patented their BRACAnalysis product to identify women at high risk for breast & ovarian cancer. Dx testing. -Myriad's test was exclusively theirs & expensive. No ability to be retested by another source even if MD ordered it. Patent set to expire in 2014. ~2000 genes were patented in US in 2012. -Supreme Court June 2013: "Naturally occurring DNA is not patent eligible, but cDNA is because it is not naturally occurring."
Describe the process of transcription
-Addition of Cap and Tail -Introns removed -Exons spliced together
How do genetic changes that underlie oncogenesis alter fundamental properties of cells?
-Allow cells to evade normal growth controls. -Acquire drive to proliferate that does not require an external inducing signal. -Fail to sense signals that restrict cell division. -Continue to live when they should die. Become immortal. -Often change their attachment to surrounding cells or extracellular matrix (ECM). -Metastasize. -Tumors are characteristically hypoxic so must obtain a blood supply. Induce growth of blood supply, i.e., (angiogenesis).
What does Immunotherapy CAR-T Therapy do and what strategies does it employ
-An array of new strategies: monoclonal antibodies to attach to & block antigens that cancer cells use to grow & spread. -Development of monoclonal antibody drugs to block checkpoint molecules. Critical to turn off continued attack once infection over. -The checkpoints are now turned off so that T cells can continue to attack cancer cells. -Effective CAR-T cells: extract from patient & train to attack cancer. -Only effective for some patients. 1st patients in 2010: still cancer free.
What is "Count Me In"? (and what is its goal)
-Began 2015 with Metastatic Breast Cancer (MBC Project). -Committed to patients having active voice in decisions & open access to researchers worldwide. De-identify patient data. -6000 patients, goal to get 100,000 participants. Projects include: Metastatic Breast Cancer - 2015 Angiosarcoma Project - 2017 Metastatic Prostate Cancer Project - 2018 Gastroesophageal Cancer Project - 2020 Others to launch soon. Supported by: Broad Institute of MIT & Harvard Dana-Farber Cancer Center Biden Cancer Initiative Emerson Collective, CA-based social change organization.
Most cancers are caused what?
2-8 sequential alterations over 20-30 yr.
How many types of cancer are there? How many genetic causes are there? Can some display as or be treated the same way?
200 types of cancer, each with different genetic cause, symptoms, & treatments.
How many nucleotides are needed to encode 1 amino acid?
3
What is the minimum # of nucleotides to encode for 10 aa?
30 maybe? must find out more
What was the logic behind the 3 letter code (codon)?
4 N x 2 letter code = 42 or 16 aa. Not enough . 4 N x 3 letter code = 43 or 64 aa. Duplicates, start & stop codons. 4 N x 4 letter code = 44 or 256 aa considered superfluous
Answer with rough estimate of a number E. coli copies it entire genome _________ base pairs in ________(time). Human cells with __________ base pairs in _______(time).
4.6 million, ~20-25 min, 6 billion, ~3-4 hours
Describe a normal human karyotype
46 chromosomes: 22 pairs autosomes plus X & Y chromosomes.
Karyotype
A display of the chromosome pairs of a cell arranged by size and shape.
DNA ligase
A linking enzyme essential for DNA replication; catalyzes the covalent bonding of the 3' end of a new DNA fragment to the 5' end of a growing chain.
What is the epigenome?
A multitude of chemical signals that can tell a genome what to do but not through DNA sequence directly
Immunotherapy CAR-T Therapies use what to fight the cancer?
A person's immune system
What is a kinetochore?
A protein complex on each side of centromere where kinetochore MTs attach
DNA helicase
An enzyme that unwinds the DNA double helix during DNA replication
Why is Angelina Jolie relevant to the fight against cancer?
Angelina Jolie (2015) after learning that she had a significant elevated risk of developing breast cancer was genetically tested. Underwent double mastectomy. Became strong advocate of making testing available to all.
Where are the Sense and antisense strands in DNA replication?
Antisense is top blue half and sense is bottom blue strand
What is an autosome?
Any chromosome that is not a sex chromosome
Tumor suppressor genes are activator or suppressors?
Both
Radioligand therapy
By harnessing the power of radioactive atoms and applying it to advanced cancers through radioligand therapy, RLTs are able to deliver radiation to target cells anywhere in the body. The goal of the targeted approach is to limit the damage to surrounding tissues.
CANCER AND CHECKPOINTS (explain the relationship)
Cancer cells can avoid destruction by taking advantage of a switch on the T-cell called an immune checkpoint. The checkpoint can shut down the T-cell and suppress the immune response, allowing the cancer to grow undisturbed.
What type of trait is most common in Epigenetic Inheritance?
Chemical modification of histones or DNA bases
Chromosome
DNA + proteins Chromatin
DNA is a two strands or a single strand?
DNA is a single continuous strand
DNA Abnormalities include....
DNA mutations, rearrangements, deletions, amplifications, & addition or removal of chemical modifications.
Development of Cancer usually due to ________ . (a single mutation? multiple mutations? )
Development of cancer usually occurs from an accumulation of mutations
CHECKPOINT INHIBITORS (what are they)
Drugs known as checkpoint inhibitors can physically block the checkpoint, which frees the immune system to attack the cancer. A single T-cell can kill thousands of cancer cells.
Watson & Crick model predicted what?
Each of the two daughter cells would have a parental strand and a new complementary strand in DNA replication
DNA polymerase
Enzyme involved in DNA replication that joins individual nucleotides to produce a DNA molecule
EGF is what?
Epidermal Growth Factor, it is one of a group of growth factors that stimulate cells to divide
What is the most common type of cancer?
Excluding cancers of the skin, breast cancer is most common cancer in women. Accounts for one of every three cancer diagnoses
The Cancer Genome Atlas (TCGA) & the Cancer Moonshot goals are...
Exploit cancer genome for early detection strategies & treatment
What phase in the cell cycle is considered most important and why?
G1 is considered most important because if not satisfied, cells enter G0. (not necessarily bad, cell-type dependent)
What is G1 of the cell cycle?
G1: Interval ("Gap") of cell growth prior to DNA replication. Biosynthesis of proteins, CHO, and lipids
Describe the cell cycle
G1: Interval ("Gap") of cell growth prior to DNA replication. Biosynthesis of proteins, CHO, and lipids •S: DNA replication is completed but is still chromatin. •G2: Interval after DNA replication. Cell prepares to divide. •M Phase or Mitosis •Cytokinesis begins before completion of telophase. •Each of 2 daughter cells enters interphase or G1.
Name some newer oncology breakthroughs
Genetic testing - A Game Changer Discovering new mutations & combinations not seen previously Targeted Immunotherapies - using immune system CAR-T cell therapy to different cancer types. Strategies to increase effectiveness & speed to engineer the cells. Finding & Treating Cancer at the same time New types of radiation therapy. Increasing Diversity in Clinical Trials Clinical trial diversity targeted to receive funding. Funding for health equity research. The Promise of PIPAC PIPAC: pressurized intraperitoneal aerosol chemotherapy Multiple areas in abdominal area. Delivers chemotherapy directly to area & direct contact with tumors.
Why is the Pan-cancer study important?
Identified 20 cancer targets / now 33 types 825 patients & 348 labs / now >22,000 15-20% can be matched to specific drugs 1st results published Fall 2013.
What is the immune system and what does it do?
Immune system is a collection of organs, specialized cells, & molecules that respond to threats from infectious organisms. While it can attack cancer, most cancers have an array of escape mechanisms to avoid detection.
Francis Crick
In 1958, Francis Crick defined the Central Dogma as the one-way flow of information: DNA to RNA to protein.
What is Epigenetic Inheritance?
Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence of the genome. (Frequently, chemical modification of histones or DNA bases)
Who won the 2018 Novel Prize in Medicine and what was their novel hypothesis that changed how cancer is treated?
James P. Allison and Tasuku Honjo they enabled immunotherapy by discovering that T-cells don't attack cancer cells due to their use of the immune checkpoint they then made drugs targeting the checkpoints to block them from being used so T-cells can continue attacking the cancer cells
What serves as "regulators of the cell cycle"?
Many proto-oncogenes are regulators of the cell cycle.
What stage of mitosis contains a checkpoint?
Metaphase
When is the karyotype acquired?
Metaphase
How many origins of replication are along a DNA strand? (0, 1, or more than 1?)
Multiple
Does the epigenome work directly through the DNA sequence?
No, it can tell a genome what to do but not through DNA sequence directly
What are the downsides of chemotherapy?
Nonspecific, kills or slows the growth of fast-growing cells but also healthy cells like those responsible for regenerating gastrointestinal lining. Radiation downsides are similar
Which cancer treatments specifically target cancer at cellular or molecular level?
Only targeted cancer therapies, Precision Medicine.
Precision Medicine
Precision Medicine, medicine based on genome of individual tumor & person.
Okazaki fragments
Small fragments of DNA produced on the lagging strand during DNA replication, joined later by DNA ligase to form a complete strand.
What are the start and stop codons?
Start: AUG Methionine 3 Stop Codons: UAA, UGA, UAG
What are the downsides of surgery for treating cancer?
Surgery is invasive and can only remove the tumor, not metastasizing cancer cells. And a surgeon can only remove what he/she can see.
T-CELLS (what are they?)
T-cells are a type of white blood cell that can identify and kill infected, damaged or cancerous cells. Each T-cell has clawlike receptors on its surface that can recognize and lock onto antigens, foreign or abnormal protein fragments on the surface of infected or cancerous cells.
Mary-Claire King proposed what?
That everyone should have access to genome sequencing to determine whether there are key mutations in BRCA1 & BRCA2. And insure should pay (most insurance companies do pay for the screening if warranted.)
ACTIVATING A T-CELL (explain how)
The T-cell must be activated before it can find and attack cancer cells. A specialized cell presents the T-cell with an antigen from a cancer cell, along with a co-stimulator protein. The T-cell begins to hunt down and kill any cells that are covered with the same antigen.
What is PPI mapping?
The comprehensive mapping of protein-protein interactions (PPIs) is highly desired for one to gain deep insights into both fundamental cell biology processes and the pathology of diseases.
What is congression?
The directed movement of the chromosomes into position at the metaphase plate is termed as congression
The BRCA1 or BRCA2 genes are important why. (and how are they related)
The proteins made by both genes are essential for repairing DNA. BRCA1 & BRCA2 are unrelated proteins, but both are normally expressed in the cells of breast & other tissues. Mutations in those genes are also associated with cancer.
Metastasis
The spread of cancer cells beyond their original site
Who was George Gamow and why was he important?
Theoretical Physicist George Gamow predicted 3-letter code (codon) required to encode the 20 amino acids. It is mRNA sequence.
How many nucleotide bases are there? How many amino acids?
There are four nucleotide bases and 20 amino acids.
Checkpoint mechanisms at each stage that tell the cell to do what? (and what is their function?)
They tell the cell to wait until a series of events have been met. Their function is to ensure accuracy & fidelity in chromosome replication & segregation.
actin
Thin filaments. (a globular protein that links into chains, two of which twist helically about each other, forming microfilaments in muscle and other contractile elements in cells.)
Myriad
Tried to patent a gene but were ruled against
RNA uses ________ not ______
Uracil, Thymine
What are neutrophils and why are they important?
White bloods cell that can migrate, they are important because Metastasis uses the same cytoskeletal machinery as neutrophils
Are ALL cancers considered to be genetic diseases?.
Yes (and/or diseases of the genome)
What is an oncogene?
altered gene that causes cancer.
Defects in the checkpoints can result in what?
aneuploidy & cancer
RNA polymerase reads the ___________ DNA strand which is also the __________ DNA strand
antisense, non-coding
What is true? a) Cytokinesis occurs before telophase b) Telophase occurs before cytokinesis c) Telophase occurs at the same time as cytokinesis d) Cytokinesis only occurs in mitosis, not meiosis
c) Telophase occurs at the same time as cytokinesis
Genetic alterations ____ (can or cannot?) be inherited from parents, and are caused by ___________, and/or occur during ___________.
can, environmental factors, cell division
Tumor suppressor genes inhibit what?
cell division
For a long time & even today, standard treatments for cancer included____________, _____________, & _____________. Each with significant downsides.
chemotherapies, surgery, & radiation therapies
What are the most common solid tumor locations and mutations?
colon, breast, brain, pancreas 33-66 genes display somatic mutations, most single-base pair substitution
What is chemotaxis?
directed movement of cells in response to concentration gradient of a substance or extracellular signal. Growth factors.
James Allison and Tasuku Honjo
discovery of cancer therapy by inhibition of negative immune regulation
Cancer genes function through ________ signaling pathway/s (one, tens, hundreds?)
dozens
DNA must carry the information contained in the genes that...
enables expression of an organism's phenotype.
DNA chemical changes can influence the ____________.
epigenome
Every individual tumor is distinct with regard to _______________, but _____________ in different tumors can be similar. Ex. There are __ genetically distinct types breast cancer.
genetic alterations, pathways affected, 4
BRCA1 & BRCA2 mutations are usually what?
insertions or deletions of a small number of DNA based pairs in the gene
Oncogenic signature is or isn't based on the tissue where occurs?
it is NOT
What does hypoxic mean?
low [O2] levels
DNA has a mechanism for transcribing DNA sequence into a __________________, which in turn translates the DNA sequence into an _______________ that results in a ____________ that folds to _____________.
messenger RNA (mRNA), amino acid sequence, polypeptide, yield a protein
What does DNA replication require? (in terms of enzymes and the DNA molecule)
multiple enzymes to untwist & unwind the DNA molecule, to separate & replicate both strands simultaneously and rapidly
Cancer cells behave abnormally because of __________.
mutations that occur
What is a proto-oncogene?
normal gene that when mutated can cause cancer.
Centromere
region where sister chromatids held together.
Daughter strands in DNA replication are synthesized ____________(one at a time or at the same time?) from ___ to ____
simultaneously 5′ to 3′
Cancers typically derive from _________
single cells
Nucleotides are added only to what end of the DNA strand?
the 3′ end (-OH).
angiogenesis
the formation of new blood vessels
Oncogenesis
tumor forming
Cancer genes include _______________ & ________________.
tumor suppressors & oncogenes
Why do tumor cells need an oxygen supply?
tumors are hypoxic
Changes in DNA can alter cell behavior, causing
uncontrollable growth & malignancy.
The proteins encoded by tumor suppressors prevent what?
uncontrolled cell growth... (signal transduction pathways and therefore gene expression are tightly regulated)
How many genes are known whose mutations drive cancer.
~140
What happens immediately after M of the cell cycle?
•Each of 2 daughter cells enters interphase or G1.
What is G2 of the cell cycle?
•G2: Interval after DNA replication. Cell prepares to divide.
Targeted Protein Degradation
•Inactivating proteins is just as important for proper cell function as activating them in the first place •We've seen phosphorylation, dephosphorylation, GTP hydrolysis, etc. as mechanisms for protein inactivation •A common (and permanent) way to inactivate proteins is to specifically target them for proteolytic degradation
What is M of the cell cycle?
•M Phase or Mitosis •Cytokinesis begins before completion of telophase.
what is the S of the cell cycle?
•S: DNA replication is completed but is still chromatin.
