Unit 2 Flashcards
What is the sequence from DNA to Protein?
Replication, transcription, and translation
What is DNA replication?
DNA is separated (unzipped) and two new strands are formed using each previous strand to create 2 exact copies
What is transcription?
DNA to RNA; mRNA
What is translation?
RNA to a protein; tRNA
Define retrovirus
Viruses that use RNA as their genetic material and carry code for enzyme reverse transcriptase; converts RNA to DNA
Define gene polymorphism
Change in the sequence of DNA which then results in a change in the sequence of mRNA
What is a silent mutation?
A mutation that doesn’t change the primary protein sequence
Define Mutations
Any inherited alteration of genetic material; noticeable changes in the organism
What is an example of a favorable mutation?
Sickle Cell Anemia in Africa; protects against malaria
List the 3 types
Point mutations, frameshift mutations, and base-pair substitution
What is a point mutation?
A mutation that doesn’t change the reading frame; change only one single base
Can point mutations be silent?
Yes they don’t always change the protein sequence; silent mutation
What happens when the protein sequence is changed in a point mutation?
Missense mutation or nonsense mutation
What is a missense mutation?
Changing of one base changes one amino acid to another
What is nonsense mutation?
Changing of one base changes the codon from an amino acid to a stop codon resulting in a short protein
What is a frameshift mutation?
Insert or delete one or more base pairs in the reading frame shifting everything
Can frameshift mutations be silent?
No
What is a base-pair substitution?
One base pair is replaced by another
Can a base-pair substation be silent?
Yes if the substitution does not change the amino acid; silent substitution
What is a mutagen?
Agents that are known to increase the frequency of mutations
Give some examples of mutagens
Ionizing radiation, chemical agents, UV radiation, viruses
What is a mutational hot spot?
Some regions of the DNA that are weak and often mutated
What is a karyotype?
An ordered display of chromosomes from largest to smallest; best done during metaphase of Mitosis
Define homologous chromosomes
Nearly identical chromosomes; the same number 5 and 5
Define non-homologous chromosomes
Non-identical chromosomes; different number 9 and 22
How can we detect chromosomal abnormalities in the fetus?
Amniocentesis and Chorionic villus sampling
Define euploid
Cells that have a multiple of the normal number set (23) chromosomes; 23 x ____
Define haploid
One set of 23 chromosomes (sex cell)
Define diploid
Two sets of 23 chromosomes; 46 total (somatic cell)
Define polyploid
When a euploid has more than the diploid number of chromosomes; still contain a multiple of 23 chromosomes
Define triploid
Three sets of 23 chromosomes; 69 total - fetus will not survive
Define tetraploid
Four sets of 23 chromosomes; 92 total - fetus will not survive
Define aneuploidy
Cell that does not contain an exact multiple of 23 chromosomes; 45 or 47 total
Define trisomy
Cell containing three copies of one of the chromosome “pairs”; 47 total
Define monosomy
Presence of only one of any of the chromosomes “pairs”; 45 total
What is disjunction?
The process of splitting chromosomes into equal amounts of genetic material to each gamete
What is nondisjunction?
An error in which homologous chromosomes or sister chromatids fail to separate normally during meiosis or mitosis; gives rise to aneuploidy
Give an example of autosomal aneuploidy
Down Syndrome (trisomy 21)
Name characteristics of Down Syndrome
Low nasal bridge, round face, long and flat tongue, low set ears, short stature, heart defects, and respiratory defects
Give examples of sex aneuploidy
Turner’s Syndrome (monosomy X), Triplo-X (trisomy XXX), and Klinefelter’s Syndrome (trisomy XXY)
Name characteristics of Turner’s syndrome
Sterile, short, webbed neck, widely spaced nipples, little body hair, and underdeveloped breasts
Name characteristics of Triplo-X
Sterile, menstrual irregularity, and mental retardation (gets worse with more X’s)
Name characteristics of Klinefelter’s syndrome
Male appearance, female-like breasts, small testes, sparse body hair, and long limbs (gets worse with more X’s)
List chromosomal structure abnormalities
Breakage, deletions, inversions, duplications, and translocations
Define chromosomal breakage
If a chromosome breaks, physiological mechanisms will usually repair it; breaks can heal in a way that alters the structure of the chromosome
What is a clastogen?
Agents of chromosomes breakage
Give some examples of clastogens
Ionizing radiation, chemicals, and certain viruses
Define deletions
A breakage resulting in loss of DNA
Give an example of a deletion
Cri du chat (cry of the cat)
What is Cri du chat?
Deletion of short arm (p) of chromosome 5
Name characteristics of Cri du chat
Low birth weight, mental retardation, microcephaly (small head), and shrieking cry
Define inversions
Breakage followed by a reversal of the fragment during re-insertion (putting piece in backwards)
Define duplications
Replication of a gene sequence resulting in an amino acid sequence being repeated multiple times
What happens if duplication occurs in the same region as Cri du chat?
Mental retardation occurs, but no physical abnormalities
Define translocation
Interchange of material between non-homologous chromosomes (13-4, 2-5); from one place to another
When does translocation occur?
When two chromosomes break and the segments are rejoined in an abnormal arrangement
Define gene
Segment of DNA that codes for a protein or regulatory molecule
Define locus
The physical (geographic) location of a gene along a chromosome
Define allele
Different form (copy) of a particular gene
Define homozygous
Two alleles of a particular gene on a pair of homologous chromosomes are identical
Define heterozygous
Two alleles of a particular gene on a pair of homologous chromosomes are not identical
Define genotype
Genetic make-up of an organism; what they have
Define phenotype
Visible observation or tested for; what they show
Define carrier
can pass “bad” gene to their offspring but are not affected themselves
Define proband
The first in the family to be seen in a health care facility and diagnosed with the disease
What is recurrence risk?
The probability (%) of a family with a specific genotype having a child with an expected phenotype
Define penetrance
The proportion of individuals of a particular genotype that expresses its phenotype in a specific environment; how many people with the disease actually show it
Define Expressivity
Relative capacity of a gene to affect the phenotype of the organism of which it is part; how much of the disease an individual shows
What is a polygenic trait?
Trait that involves multiple genes
Give an example of a polygenic trait
Hair color, height, and eye color
Other than genetic alterations what else has influence over disease and disorders?
Diets, habits, and exposures (environment)
Give an example of diseases due to environment
Colon cancer is more common in the US and Stomach cancer is more common in Japan
What is multifactorial inheritance?
Responsible for the greatest number of people that will need special care because of a genetic disease
Give some examples of multifactorial diseases?
Atopic reactions, diabetes, cancer, spina bifida/anencephaly, pyloric stenosis, cleft lip, cleft palate, congenital hip dysplasia, club food, and more
Define multifactorial trait
Traits follow a bell-shaped curve because they are influenced by both the environment and genetics
Give some examples of multifactorial traits
Blood pressure, serum cholesterol, or all the values reported in a blood chemistry panel
What is the Threshold model?
Model used to describe multifactorial traits/ you either have them or you don’t
Define liability in the Threshold model
As the number of genetic and/or environmental risk factors increase, so does the liability for that disease; when it is so great that it reaches a threshold, an abnormality disease results
How are liability and threshold related?
They are inversely proportional; as liability increases your threshold decreases
How does the recurrence risk increase?
More than one family member is affected (sibling risk), expression of disease in proband is more severe, and proband is less common than affected sex
How does the recurrence risk decrease?
If the disease is expressed in more remotely-related relatives
Define tumor
Growth of tissues caused by the uncontrolled replication of cells
Define neoplasm
New and abnormal development of cells that are unresponsive to normal growth control mechanisms; may be benign or malignant
Define cancer
Invasion of surrounding tissues that have the ability to travel to, and proliferate at distant sites (metastasis)
Benign vs Malignant
Benign: slow growth, encapsulated, non-invasive, well differentiated, low mitotic rate, and does not metastasize
Malignant: rapid growth, non-encapsulated, invade local structures and tissues, poorly differentiated, high mitotic rate, and metastasize
How are tumors named?
According to their tissue of origin with the suffix “-oma”; benign tumors have simpler names than malignant ones
Give examples of benign tumor names
Lipoma (fatty), fibroma (fibrous), osteoma (bone), and chondroma (cartilage)
Give examples of malignant tumor names
Fibrosarcoma (fibrous connective), Chondrosarcoma (cartilage), Hemangiosarcoma, Squamous carcinoma (epithelial), glioblastoma (glial cells), and retinoblastoma (retina)
What is Carcinoma in situ (CIS)?
Pre-malignant or pre-invasive epithelial malignant tumor that is localized in the epithelium and hasn’t broken through the basement membrane
Define transformation
Process by which a normal cell becomes a cancer cell; not a single event
Define anaplasia
Loss of differentiation and organization; doesn’t look like a cell anymore
List histological features of cancer cells
Bizarre nuclei, cell shape, and sizes due to rapid cell division, invasion of the basement membrane, de-differentiation (more like embryonic cells), cellular or extracellular accumulations; build up (“mucus lakes” in lung cancer), and necrotic debris
Lis abnormal gene expression in cancer cells
Turn on genes that: guide the cell through the cell cycle (violate check points), bring blood vessels to the cell (angiogenesis), and helps the cancer cell move to places it doesn’t belong (dissolve connective tissue barriers and move in and out of blood vessels)
Define oncogenes
Cancer genes
Explain the multi-hit model of carcinogenesis
Carcinogenesis is a multi-step process characterized by age and exposure to environmental agents/carcinogens that results in inactivation of tumor suppressor genes and amplification of oncogenes
Step 1 of multi-hit model
Inactivation of APC tumor suppressor gene resulting in dysplastic epithelium and then early adenoma
Step 2 of multi-hit model
Activation of K-ras oncogenes (growth factor) resulting in intermediate adenoma
Step 3 of multi-hit model
Inactivation of tumor suppressor gene 18q resulting in late adenoma
Step 4 of multi-hit model
Inactivation of TP53 tumor suppressor gene (tells cells to do apoptosis) resulting in carcinoma
Step 5 of multi-hit model
Inactivation of other tumor suppressor genes resulting in metastatic cancer
Where does cancer usually occur?
In body cells that are constantly dividing through out life (skin, bone marrow, intestinal lining, etc.)
What is the Philadelphia chromosome?
Occurs in Chronic myelogenous leukemia (CML) there is translocation between chromosome 9 and 22; doesn’t make normal proteins
Define tumor markers
Biological markers (tags) produced by cancer cells: cellular products, antigens, or alteration of the genes or chromosomes
Give examples of tumor markers of cellular products
Hormones, antibodies, and enzymes
Give an example of tumor markers that are antigens
Tumor-Specific Antigen (TSA)
How do we indicate the presence of cancer?
If a tumor marker leaks into the blood, CSF, or urine, or if we get a sample of the cells from the cancerous tissue
What else can we use tumor markers for?
To screen and identify people at a high risk of cancer, diagnose specific types of tumors, follow the clinical course of cancer
What do tumor markers often lack?
Specificity, sensitivity, predictability, and feasibility
Tumor marker example: Hormones
“Ectopic” (out of place) hormone production is the production of hormones by tumors of non-endocrine origin; ACTH, HCG, HGH, ADH, TSH, epinephrine, and norepinephrine
Tumor marker example: Enzymes
Cancers don’t produce new enzymes; instead we find abnormal levels of normal enzymes. These are usually only detected in the blood when the tumor is large or metastasis has occured
Tumor marker example: Antibodies
Produced by some cancers; multiple myeloma
Tumor marker example: Tumor-specific Antigens
Cancer cells express “non-self” flags; HER2/neu
Tumor marker example: Viral tumor-specific antigens
Produced and expressed by virally-transformed cells
Tumor marker example: Oncofetal tumor-specific antigens
Expressed by cells during embryonic development but are absent or low in normal adult cells; fetoprotein in hepatic, pancreatic, and epithelium cancers, and carcinoembryonic antigen (CEA) in colonic, pancreatic and breast tumors
Tumor marker example: Protein tumor-specific antigens
Function in proliferation, enzymatic processes, as receptors, and cellular structures; Prostate-specific antigen (PSA)
What is PSA?
Glycoprotein produced by the prostate whose values are related to prostate mass; a tumor cell marker (TCM) used as a screening test for prostate cancer; blood test
Define paraneoplastic syndrome
Signs and symptoms unrelated to the local effects/presence of the neoplasm caused by substances released from the tumor to an immune response to the tumor
Examples of paraneoplastic syndrome
Hypercalcemia in breast and renal carcinomas from PTH-related protein, Polycythemia in cerebellar hemangioma and hepatocellular carcinoma from erythropoietin, and Hypoglycemia in hepatocelluar carcinoma from insulin like substance
Define anchorage-indpendence
Continued growth even when unattached from the original tissue; free moving
Define autonomy
Cancer cell’s independence from normal cellular controls; grow on their own without regards to other cells
What are proto-oncogenes?
Unaltered, normal health alleles of genes that control/regulate cellular growth and differentiation
What are oncogenes?
Is a proto-oncogene that has been altered (mutate) by carcinogenic agent; cancer gene
What are tumor-suppressor genes?
Encode for proteins that inhibit cell division; anti-oncogenese, fight cancer
How can can occur?
Either by the activation of oncogenes or the inactivation of tumor-suppressor genes
Define loss of heterozygousity
Patient is born a carrier; has one mutated gene that is recessive, the second copy (normal) of gene mutates and now you have two bad genes –> cancer
Give an example of genetic alterations in cancer
p53 (tumor-suppressor) gene mutations; hypoxic environments will activate p53 TS with activates p53 protein to activate apoptosis, but in cancer p53 gene is mutated so abnormal cells can proliferate
List contributors to cancer growth
Autocrine stimulation, immortality, angiogenesis and angiogenesis
What is autocrine stimulation?
Cancers have the ability to secrete and respond to their own growth factors; increased expression of growth factor receptors, cancer cells create numerous copies of genes and expression of gene products (HER2/neu - breast cancer and bcr/abl - tyrosine kinase in CML)
What is immortality?
The only cells in the body that are immortal are stem cells; telomeres are protective end-caps of chromosomes that are maintained by telomerase, as telomeres are lost cell loses ability to divide, but cancer cells can activate telomerase which keeps the cells in place and keeps them growing
What is angiogenesis?
Process that results in new blood vessels which allow cancers to enlarge
List genetic alterations
Point mutations, translocation, and gene amplification
What is a point mutation?
A small base-pair change can result in a normal proto-oncogene becoming an unregulated oncogene; translocated either increases synthesis or fusion of a gene
What is translocation?
Part of chromosome is replaced by a part of a different chromosome; 8 and 14 - burkitt’s lymphoma and 9 and 22 - CML (philadelphia)
What is gene amplification?
Instead of two copies of a given gene there may be hundreds of copies; over expression of an oncogene
What are cancer stem cells?
Cells that divide to give rise to more cancer cells; parent cancer cell that are often based on cell surface markers “CD”
What does CD stand for?
Cluster of differentiation
What do we do with cancer stem cells?
We tag them with a florescent light to mark each one
Define stroma
Original tissue cancer started in; house
What are the interactions between cancer cells and stoma?
Normally growth factors and adhesive proteins in the surrounding connective tissue and blood vessels keep cells from going “off the reservation”, but in cancer cells begin to express genes that allow them to divide uncontrollably and move freely in stroma = carcinoma in situ, next step eats through basement membrane = carcinoma
How does chronic inflammation increase cancer?
Inflammatory cells release cytokines to stimulate cellular proliferation, angiogenesis, and promote healing so they are easily mutated by cancer cells
Give some examples of cancers associated with chronic inflammation
Colon cancer, liver cancer, and lung cancer
What is an oncogenic virus?
Viruses that change the genetic makeup of the cell, which results in the alteration of the daughter cell
Give examples of oncogenic viruses
Epstein-barr virus (EBV) - hodgkin lymphoma, burkitt lymphoma, Human Papilloma virus (HPV) - cervical cancer, HIV - kaposi sarcoma, and hepatitis B virus (HBV) - hepatocellular carcinoma
What are oncogenic bacterium?
Bacteria that can cause cancer
Give an example of an oncogenic bacterium
Helicobacter pylori - bacteria that infects stomach; common causes are peptic ulcer disease, gastric lymphomas, and gastric carcinomas; think chronic inflammation
Define metastasis
Spread of cancer from the initial site of neoplasm development to distance tissues of the body; sequence of events
Step 1 of metastasis: detachment
Cells break loose from their original location
Step 2 of metastasis: invasion
Cellular proliferation, barrier destruction, secretion of proteases and protease activations - degrades basement membrane, increased motility
Step 3 of metastasis: intravasation
passage into vessels (blood or lymph)
Step 4 of metastasis: adherence in favorable sites
certain types of cancerous cells have a preference for specific organs; organ tropism - encouraged by growth factors, hormones, presence of tumor receptors, and route
Step 5 of metastasis: extravasation
Leaves blood or lymph and invades secondary tissue
Step 6 of metastasis: colonization
establishment in new tissue
Sequence of metastasis
Local transformation and extension, motility, angiogenesis, invasion, intravasation, adherence at favorable site, extravasation, and colonization
Stage 1 cancer
Neoplastic cells in original site, well differentiated cells
Stage 2 cancer
Metastatic cell in original site and local lymphatics, moderately-differentiated cells
Stage 3 cancer
Cells in original site and distant lymphatics, poorly differentiated cells
Stage 4 cancer
Metastatic cells are found in many body areas, very poorly differentiated cells
List systemic effects of neoplasms
Vessel invasion (bleeding), lymphatic invasion (lymphedema), nerve invasion (pain, numbness, tingling), bone cortex invasion (pain and fracture), bone marrow invasion (pancytopenia, infection, bleeding), and liver invasion (hepatic insufficiency)
List clinical manifest ions of cancer
Pain, fatigue, anemia, infections, and cachexia syndrome
Pain
little or no pain = early malignancy, influenced greatly by fear, anxiety, sleep loss, and psychological responses. Pressure on sensitive structures, obstruction, severe stretching of tissues, terminal cancer = severe pain
Fatigue
Sleep disturbance, biochemical changes to treatment, diminished activity level, nutritional status, and necrosis factors
Anemia
Reduction in red blood cell numbers caused be chronic bleeding, malnutrition, therapies, malignancy in blood-forming organs; also leukopenia and thromboycytopenia from malignancy in bone marrow
Infection
Most common event leading to demise of patient with malignancy - reduction in immunologic functions due to treatment regimens, poor wound care, and compromised patient care
Cachexia syndrome
Ill health, wasting, emaciation and decreased quality of life. Symptoms = reduced sweet, sour, salty sensations, decreased appetite, weight loss, altered metabolism
Treatments for cancer
Chemotherapy, radiation, and surgical therapy
Chemotherapy
Destroy cells that are in stage of vulnerability, eliminates enough cells for the immune system to take care of the rest (cocktail of drugs), targeted therapy - enzyme inhibitors, monoclonal antibodies which direct at a specific tumor antigen
Radiation
Damages DNA of the rapidly dividing neoplastic cells
Surgical therapy
Excisional, debulking, palliative - useful when tumor has not passed beyond stage 3, tumor and anything infected lymph node must be removed
