MBB 446 Lecture 1 Flashcards
What is cancer?
- Cancer is the abnormal growth of cells
- Cancer cells continue to divide (proliferate) in an uncontrolled manner
How does cancer start?
Cancer starts with a single abnormal cell; i.e. it is clonal
Describe doubling time for cancer (2)
- Doubling time: the rate at which cells divide (various for cancer cells)
- Vary btwn weeks and months
- 20 doublings = 1 million cells (cell mass is the size of a pinhead and is undetectable);; this is called the “silent” period and can last for years 30 doublings = 1 billion cells (cell mass is now a lump detectable by palpation, X-ray, imaging)
How many cells is 20 doublings? What is the size? Can it be detected, if so how?
- 20 doublings = 1 million cells
- cell mass is size of a pinhead and is undetectable
- this is called the “silent” period and can last for years
How many cells is 30 doublings? What is the size?
- 30 doublings = 1 billion cells
- cell mass is now a lump detectable by palpation, X-ray, imaging
Green word for non-ulcer forming tumor?
Carcinos
Greek word for ulcer-forming tumors?
Carinoma
What is the Latin word for crab?
Cancer
Greek word used to describe swelling of tumors?
Oncos (origin of word oncologist)
How many types of cancer are there?
More than 200 different types of cells in our bodies so more than 200 types of cancer
What are the 4 most common cancers?
breast, prostate, lung and colorectal
Slide 23
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What is the ploidy of human genome?
Diploid
What are alleles?
Different versions of a gene
What does dominant and recessive refer to?
These terms refer to alleles of a gene, or to phenotype e.g. an allele that expresses its phenotypic effect even when heterozygous is dominant
What is homozygous with respect to a gene?
If an organism carries two identical alleles of a gene
What is heterozygous with respect to a gene?
If an organism carries two different alleles of a gene
What is hemizygous with respect to a gene?
single allele only (eg. X chrom in males; or when one allele is deleted)
What is SNP?
- Single Nucleotide Polymorphism
- DNA sequence variant that occurs in a single nucleotide; must occur in > 1% of the population to be considered a SNP
If frequency is lower than 1%
then allele is regarded as a “mutation”
What is euploid karyotype?
Normal configuration of chromosomes (ie. complete chromosome set) (22 autosome pairs; sex chromosomes)
What is aneuploidy?
Deviation from the euploid karyotype
Chromosome _____ can create a genetic configuration that somehow benefits a cancer cell
gains or losses
Slide 29
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What is SKY analysis?
Spectral Karyotype analysis (chromosome painting)
Slide 32
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Define HSR
- Homogeneously staining region; repeated rounds of reduplication of a chromososome segment yields many tandem copies of the segment; extra copies may be fused head-to-tail in a long array; yields a concomitant amplification in the copy number of the genes on that segment
Define DMs
- Double minute chromosomes
- chromosomal segments that have broken loose from their original sites and replicate autonomously; increase to many copies per nucleus
Both _____ and _____ lead to gene amplification
HSRs and DMs
What is a germ line mutation?
Transmission of mutations from one generation to the next, made possible by the germ cells (sperm and egg), is said to occur via the germ line i.e. germ line transmission of a new mutation can only occur if that mutation occurred in a gene carried in the genome of a sperm or egg
What is a somatic mutation?
- Mutations affecting the genomes of cells everywhere else in the body (the soma) are somatic mutations
- Somatic mutations can affect the behaviour of the cell in which it occurs, but are not transmitted to the next generation
Which type of mutation is of central importance to cancer formation?
Somatic mutations
One way to identify potential cancer-causing mutations?
Compare the sequence of a somatic cell (e.g from tumor tissue) to germ line in the same individual. The “germline” sample is often just a non-cancerous tissue: eg. usually WBCs; or can be a skin biopsy for example
What is constitutional DNA? Example?
- the DNA in germ cells (egg and sperm cells that join to form an embryo) is also called constitutional DNA; it is the source of DNA for all other cells in the body)
What was the previous view of tumors?
are foreign bodies that were somehow established in the body of an afflicted patient
In the 19th century what was determined about cells?
- all tissues are composed of cells and cell products
- All cells arise through the division of pre-existing cells
- All cells in the body of a complex organism are members of cell lineages that can be traced back to a fertilized egg
What is histology or histopathology?
Microscopic examination of tissue sections (thin slices)
What did histology reveal about tumors?
revealed that tumors were composed of masses of cells
What is the current view of tumors?
Tumors often derive directly from the normal tissues in which they are first discovered
Slide 39
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What is dysplastic mucosa
Abnormal
What is adenocarcinioma
Tumor (invasion of underlying tissue)
Define neoplasia
New growth
What are the 2 basic components of tumors?
- Neoplastic cells that constitute the tumor parenchyma
2. Reactive stroma made up of connective tissue, blood vessels and immune system cells
In some cases, the parenchymal cells themselves stimulate the formation of what?
an abundant collagenous stroma = desmoplasia
What is desmoplasia
an abundant collagenous stroma
What is the growth and spread of tumors critically dependent on? The classification of tumors is based primarily on?
- Growth and spread dependant on STROMA
2. Classification of tumor dependant on the PARENCHYMAL COMPONENT
How does a normal mammary gland compare to an invasive ductal breast carcinoma?
Cancer cells (arising from epithelial cells) have enlarged nuclei, no longer form well-structured ducts, and have invaded the stroma
What is stroma?
Connective tissue cells (fibroblasts and adipocytes), and collagen matrix
What is the primary tumor
Site where cancer begins
What is metastases?
spread of cancer to secondary sites throughout the body; often can be traced back to the primary tumor
What are the 2 broad categories of tumors and describe each?
- Benign (local growth; no invasion of adjacent tissues)
2. Malignant (invasion of nearby tissues and metastases)
Which type of category is majority of tumors?
Benign
Are benign tumors harmful? If so when?
Harmless except where expansion can press on vital organs, or alter hormone levels
What is the % of cancer-related mortality from malignant tumors
90%
Scheme for classifying tumors depends on what 3 main determinants of tumor biology? Describe each
- Differentiation state:
- Epithelial, Nonepithelial, or Mixed - Embryonic origin (Ectoderm, Endoderm, Mesoderm) and normal cell-of-origin (e.g. breast cell, lung cell)
- Biological behaviour: extent of progression to a highly malignant state (e.g. benign vs malignant; stage of progression)
Define tumor
Any abnormal proliferation of cells
Define benign
- not cancerous; non-malignant; usually not dangerous to health
What suffix is attached to benign tumors? Example?
In general, benign tumors are designated by attaching the suffix – oma to the name of the cell type from which the tumor originates;; eg. fibroma, adenoma
Define malignant
cancerous;; capable of invading surrounding tissue and spreading to other parts of the body via the circulatory or lymphatic systems (= metastasis)
What suffix is attached to malignant tumors? Example?
Designated by suffixes carcinoma, sarcoma, leukemia, lymphoma;; eg. fibrosarcoma, adenocarcinoma
What are the 2 characterisitics of a malignant tumor?
- Invasion: e.g. cancer has broken thru basement membrane and is invading surrounding tissue
- Spreading: cancer cell detached from tumor can get into bloodstream and spread the cancer to another part of the body
What are the 3 main types of malignant tumors? Describe what they malignancy they are and what % they make up of the total.
- Carcinomas = malignancies of epithelial cells (90%) (derive from all 3 germ layers)
- Sarcomas = malignancies of connective tissues (2%) (derive from mesenchyme)
- Leukemias and Lymphomas = malignancies of blood- forming cells and immune system, respectively (8%)
most human tumors arise from what tissue type and what cancer name type are they given?
epithelial tissues = the carcinomas
What are epithelia?
sheets of cells that line the walls of cavities and channels (or skin); the mature differentiated epithelial cells are at the exposed surface
What is the basement membrane or basil lamina?
a specialize type of ECM that lies beneath the epithelial cell layers; it separates the epithelial cells from the underlying layer of supporting connective tissue cells (=stroma)
Draw the basic plan of epithelial tissue?
- Epithelial cells
- Basement membrane
- Stromal cells and collagen fibres
Carcinomas include tumors arising from what parts of the body?
arising from the GI tract, skin, mammary gland, pancreas, lung, liver, ovary, gallbladder and urinary bladder
Carcinomas include cell types that arise from what 3 primitive cell layers in the early vetebrate embryo
- Endoderm (inner cell layer): lungs, liver, gallbladder, pancreas, esophagus, stomach, intestines
- Ectoderm (outer embryonic cell layer): skin
- Mesoderm (middle layer): ovaries
What are the 2 main categories of carcinomas?
- Squamous cell carcinomas
2. Adenocarcinomas
What is squamous cell carcinomas
arise from epithelial cells that form protective cell layers; epithelial sheets act to seal the cavity or channel that they line
What is adenocarcinomas
arise from specialized epithelial cells that secrete substances into the ducts or cavities that they line (e.g. often secrete substances used to protect the epithelial cell layers from the cavity contents)
What are the 2 main categories of carcinomas dependant on?
dependent on the major biological functions associated with epithelia
Can only 1 type of carcinoma exist or both?
Both can co-exist
Examples of tissue sites of more common types of adenocarcinoma
- Lung
- Colon
- Pancreas
- Stomach
- Esophagus
- Prostate
- Endometrium
- Ovary
Examples of tissue sites of more common types of squamous cell carcinomas
- Skin
- Nasal cavity
- Oropharynx
- Larynx
- Lung
- Esophagus
- Cervix
Other types of carcinomas that aren’t squamous cell carcinomas or adenocarcinomas
- Small-cell lung carcinoma
- Large-cell lung carcinoma
- Hepatocellular carcinoma
- Renal cell carcinoma
- Transitional cell carcinoma (of urinary bladder)
Slide 52
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What cells give rise to stomach adenocarcinoma?
Secretory epithelial cells, specifically mucus-secreting cells in the stomach wall
What cells give rise to colon adenocarcinoma?
Secretory epithelial cells, specifically mucus-secreting goblet cell (purple) in the small intestine
What are sarcomas?
tumors that derive from various connective tissues throughout the body; share a common mesodermal origin
What % of tumors do sarcomas constitute?
1%
What cell types are sarcomas derived from?
Derive from mesenchymal cell types including fibroblasts (secrete collagen), adipocytes (store fat), osteoblasts (form bone), myocytes (form muscle), endothelial cell precursors
What is the presumed cell lineage of founding cell from the following common sarcomes:
- Osteosarcoma
- Liposarcoma
- Leiomyosarcoma
- Rhabdomyosarcoma
- Malignant fibrous histiocytoma
- Fibrosarcoma
- Angiosarcoma
- Chondrosarcoma
- Osteosarcoma
- Osteoblast (bone-forming cell) - Liposarcoma
- Adipocyte (fat cell) - Leiomyosarcoma
- Smooth muscle cell (e.g. in gut) - Rhabdomyosarcoma
- Striated/skeletal muscle cell - Malignant fibrous histiocytoma
- Adipocyte/muscle cell - Fibrosarcoma
- Fibroblast (connective tissue cell) - Angiosarcoma
- Endothelial cells (lining of blood vessels) - Chondrosarcoma
- Chondrocyte (cartilage-forming cell)
What is leukemia?
(“white blood”) = malignancies of the hematopoietic cell lineages (dispersed single cell populations)
What is lymphoma?
include tumors of the lymphoid lineages (B and T lymphocytes); aggregate to form solid tumor masses found in lymph nodes
What are other examples of common hematopoietic malignancies besides leukemia and lymphomas?
- Acute lymphocytic leukemia (ALL)
- Acute myelogenous leukemia (AML)
- Chronic myelogenous leukemia (CML)
- Multiple myeloma (MM)
- Non-Hodgkin’s lymphoma (NHL)
- Hodgkin’s lymphoma (HL)
What are acute myelogenous leukemia cells derived from?
- Derive from precursors of the lineage that form granulocytes and monocytes
- Note small rim of cytoplasm around large nuclei of AML cells (blue)
What do neuroectodermal tumors arise from?
- Arise from cells that form components of the central and peripheral nervous system
- Originate from the ectodermal layer
neuroectodermal tumors comprise what % of cancers?
Comprise 1.3% of all cancers (but are responsible for about 2.5% of cancer related deaths)
What is the linage of founding cell from the following types of neuroectodermal malignancies:
- Glioblastoma multiforme
- Astrocytoma
- Meningioma
- Schwannoma
- Retinoblastoma
- Neuroblastoma
- Ependymoma
- Oligodendroglioma
- Medulloblastoma
- Glioblastoma multiforme
- Highly progressed astrocytoma - Astrocytoma
- Astrocyte (type of glial cell) - Meningioma
- Arachnoidal cells of meninges - Schwannoma
- Schwann cell around axons - Retinoblastoma
- Cone cell in retina - Neuroblastoma
- Cells of PNS - Ependymoma
- Cells lining ventricles of brain - Oligodendroglioma
- Oligodendrocyte covering axons - Medulloblastoma
- Granular cells of cerebellum
Define transdifferentiation
switching of tissue lineage and resulting acquisition of an entirely new set of differentiated characteristics
Example of transdifferentiation
Epithelial-mesenchymal transition (EMT): epithelial cancer cells (e.g. at the borders of many carcinomas) often change shape and gene expression programs and take on attributes of nearby stromal cells of mesenchymal origin
What often accompanies and enables the invasion of carcinoma cells into adjacent normal tissues
EMT
What are anaplastic tumors? What % of tumors does it occur in?
- Tumors have lost all of the tissue-specific differentiated traits of their normal precursor tissues; cells are said to have dedifferentiated; no longer possible to use Histopathology to identify tissue of origin
- ~ 1-2% of tumors
