10.2 Cancer Highlights Flashcards
* = also MJ slide
What are 2 origins of cancer?
1) Sporadic: genetic mutation of single somatic cell
2) Inherited (familial)
When cancer occurs as part of a ______________ cancer syndrome, the __________ cancer-causing mutation is inherited through the germline
hereditary; initial
1) The development of cancer is called what?
2) Are most cancers inherited or sporadic?
1) Oncogenesis
2) Sporadic
1) Cancer cells are clonal descendants from how many mutant cells?
2) The cell accumulates many specific mutations over a long period of time; hence, _______ as the primary risk factor for cancer
3) Cancer cells escape control of the cell cycle and begin uncontrolled division and ___________ continue to accumulate
1) one mutant cell
2) age
3) mutations
____________ is a disease process characterized by uncontrolled cellular proliferation leading to the growth of a tumor (neoplasm)
Neoplasia
For a tumor to be cancer, it must also be ______________, which means it is capable of spreading or metastasizing to other locations
malignant
What are 2 primary characteristics of cancer?
invasive and malignant
A process by which cells detach from the primary tumor and move to other sites in the body is called what?
Metastasis
Benign tumors are usually designated by adding what to cell type of origin?
“-oma”
1) What are carcinomas?
2) What is adenocarcinoma?
3) What is SCC?
1) Arise in epithelial tissue*
2) Malignant tumor of glandular cells
3) Malignant tumor of squamous cells
List where each arises:
1) Sarcomas
2) Leukemias
3) Lymphomas
1) Mesenchymal tissue
2) Hematopoietic cells
3) Lymphoid tissue
For benign tumors, describe their:
1) Growth
2) Metastasis
3) External surface
4) Capsule
5) Necrosis
6) Hemorrhage
1) Slow, expansive
2) No
3) Smooth
4) Yes
5) No
6) No
Why does a cancerous mass bleed so much?
Because it can’t create enough blood supply to supply the cells in the middle of the mass, so they die
For malignant tumors, describe their:
1) Growth
2) Metastasis
3) External surface
4) Capsule
5) Necrosis
6) Hemorrhage
1) Fast, invasive
2) Yes
3) Irregular
4) No
5) Yes
6) Yes
For benign tumors, describe their:
1) Architecture
2) Cells
3) Nuclei
4) Mitoses
5) Chromosomes
1) Resembles original tissue
2) Well differentiated
3) Normal size + shape
4) Few
5) Normal
For malignant tumors, describe their:
1) Architecture
2) Cells
3) Nuclei
4) Mitoses
5) Chromosomes
1) Doesn’t resemble tissue of origin
2) Poorly differentiated
3) Pleomorphic
4) Many irregular
5) Aneuploid
List 4 malignant tumors that sound benign
1) Lymphoma
2) Mesothelioma
3) Melanoma
4) Seminoma
List + define 2 non-tumors that sound like tumors
1) Hamartoma: mass of disorganized indigenous tissue
2) Choristoma: heterotopic mass of cells
1) Genes that initiate or maintain cell division are called what?
2) Mutant genes that induce or continue uncontrolled cell proliferation are called what?
1) Proto-oncogenes
2) Oncogenes
ras Proto-Oncogene
1) What does it do when active?
2) What does it do when inactive?
1) Transfers molecular signals from the plasma membrane to the cell nucleus and initiates cell division
2) Cell division is inhibited
1) Genes that mediate programmed cell death are called what?
2) Genes that help maintain the integrity of the genome are called what? Give an example
1) Gatekeeper TSGs
2) Caretaker genes; DNA repair genes
*Tumor suppressor genes:
1) What proteins do these encode?
2) Deletion or inactivation of these products cause cells to do what?
3) _____________ mutations in tumor suppressor genes cause cancer (Two-hit hypothesis)
1) Those
2) Divide continuously
3) Recessive
Cyclin Dependent Kinases AND Cyclin Dependent Kinase Inhibitors (CDKIs)
1) Cyclin Dependent Kinases drive the cell cycle by combining with cyclins to move from one phase to the next
2) CDKIs are inactivated in many cancers (TSGs)
1) Cyclin Dependent Kinases drive the cell cycle by doing what?
2) Cyclins are _____________ in many cancers(oncogenes)
3) While CDKIs are _____________ in many cancers(TSGs)
1) combining with cyclins to move from one phase to the next
2) overexpressed
3) inactivated
*1) ___________ is a tumor suppressor gene that monitors cellular stress (usually referred to as just ______)
2) What is activated by anoxia, inappropriate oncogene signaling, or DNA damage?
- = also MJ slide
1) TP53; p53
2) P53
1) *P53 _____________ neoplastic transformation by several mechanisms
2) List these 3 mechanisms
1) prevents
2) repair, arrest, death
*TSG Mutations Occur in both ___________ and ___________Forms
Hereditary and Sporadic
1) Cancer is initiated when a second inactivating mutation occurs in the __________ TSG allele in one cell of the body.
2) Cancer is initiated when both normal alleles are inactivated by ______ somatic events in the same cell.
1) normal
2) two
Retinoblastoma is a _______________ tumor of the eye arising in retinoblasts (embryonic retinal cells that disappear at about 2 years of age)
malignant
Because mature retinal cells do not transform into tumors, this tumor usually occurs only in _____________ and is caused by mutations in the _______ gene on chromosome ________–.
children; RB1; 13
*What are 2 kinds of retinoblastoma? Differentiate between their genetics
1) Familial (hereditary)
-one mutant copy of RB1 gene and one normal copy of the RB1 gene
-normal copy of RB1 gene acquires a spontaneous mutation
2) Sporadic
-mutations of both copies of RB1 gene occur in a single cell
*Hereditary retinblastoma
1) With hereditary retinoblastoma, there’s a _________ to _________% chance of developing the disease
2) Where/ when does it usually occur? Why?
1) 85-95%
2) Usually both eyes; because both eyes have already had one mutation, so each just needs one more mistake for disease to occur
*Sporadic retinoblastoma: When does it usually occur and why?
Usually involves one eye and has a later onset
*True or false: All patients with bilateral disease have germline RB1 mutations, but not all patients with germline mutations develop bilateral disease.
True
*Retinoblastoma is uniformly __________ if untreated, so CHECK THE ______ REFLEX!!!
fatal; RED
*Retinoblastoma:
1) Given appropriate therapy, more than ____ to ____% of patients are free of disease 5 years after diagnosis.
2) Patients with _______________ mutations have a markedly increased risk of secondary neoplasms.
1) 80% to 90%
2) germline RB1
If the disease is unilateral at the time of the patient’s presentation, the patient still needs frequent examinations to detect any new retinoblastomas in the unaffected eye because ____% of apparently sporadic cases are caused by the inheritance of a new germline mutation
30%
*Lynch syndrome:
1) A form of colon cancer that develops with very few ________, but each with a high probability of becoming _________.
2) An autosomal caretaker mutation caused by mutations in one of four DNA __________ repair genes
1) polyps; cancerous
2) mismatch
Patients with Lynch syndrome are also at increased risk for cancers of what origin(s)?
Ovary, stomach, small intestine, pancreas, upper urinary tract, hepatobiliary tract, brain, skin, and prostate
Lynch syndrome:
1) Mutations in MMR genes generate a cascade of mutations in DNA microsatellites, which does what?
2) Mutations in microsatellites that are in or near other genes disrupt what?
1) destabilizes the genome
2) the functions of those genes
Lynch syndrome: Current guidelines recommend that all patients with __________ have their tumors screened for LS, and patients with positive tumors should be offered genetic counseling and genetic testing for LS
CRC
Lynch Syndrome:
1) When should you start surveillance colonoscopy?
2) What abt transvaginal ultrasound?
1) 20-25
2) 30-35
In oncogenesis, a single cell acquires ___________ mutations and failure of regulation to become a cancer
several
Give the short version of step 1 of tumorigenesis
[mutations in] activated oncogenesis + tumor-suppressor genes = no growth factor needed, escaped cell cycle
Step 2 of tumorigenesis (short version)
Failure to stop either of the two mutations
Step 3 of tumorigenesis (short version)
Express MHC I proteins to decrease immune response
Evade CD4 T cells and NK cells
Step 4 of tumorigenesis (short version)
Antiapoptic genes don’t work,
Step 5 of tumorigenesis (short version)
Immortality is created due to antiapoptic genes not working, telomerase
Step 6 of tumorigenesis (short version)
VEGF (Vascular endothelial growth factor) leads to “All you can eat” blood supply
What is step 7 of tumorigenesis? (short version)
Metastasis
Tumorigenesis: Step 2 (Fail to regulate mutation)
a) Loss of miRNAs that fail to downregulate oncogenes leads to overexpression of the oncogene
b) Activation of miRNAs that downregulate TSGs leads to loss of TSG expression
Tumorigenesis: Step 3
MHC I presents “self antigen” to T cells + also inhibits the cytotoxic effects of Natural Killer Cells
Tumorigenesis: Step 4
Escape Apoptosis:
BCL2 normally keeps cytochrome C within the mitochondria; IAP/ “Inhibitor of Apoptosis Protein” blocks the intrinsic apoptosis cascade
(Remember, this is the means through which damaged DNA is regulated)
Tumorigenesis: Step 5
Become Immortal:
The CA cells produce telomerase to extend the life of the cell, so that senescence never occurs
Tumorigenesis: Step 6
Create Blood Supply:
1) Tumor makes VEGF
2) Tumor needs more blood; it can achieve this increased supply by getting more vessels to its site
Tumorigenesis: Step 7 (Metastasize)
1) A further consequence of VEGF expression is that _____________________ aids the spread of the tumor through local invasion and distant metastasis.
2) This happens because the cells lack polarity and are rapidly _________________
3) They are friable, therefore, and able to move to distant sites through the available blood supply, especially after passing through the local __________________________.
4) Often, the cancer cells are taken up by the _______________ system
1) neo-vascularization
2) proliferating
3) basement membrane
4) lymphatic
1) Deletion or duplication of entire chromosomes, or chromosome segments, respectively are called what?
2) Define Gene Amplification
3) The exchange of segments between chromosomes are what?
1) Aneuploidy and Aneusomy
2) Segments of chromosomes are replicated multiple times
3) Chromosomal translocations
*What are the 7 things that make cancer cells different from other cells?
They:
1) Grow and proliferate without regulation by escaping the cell cycle
2) Fail to regulate initial mutation
3) Escape our own immune System
4) Escape the Apoptosis pathway
5) Become immortal after making telomerase
6) Create their own blood supply
7) Then invade other tissues
True or false: environment can affect carcinogenesis
True
Human Papillomaviruses cause _________ cancer
cervical
Grading and staging: differentiate between them
1) Grading: Cytological evaluation of tumor
2) Staging: Size of primary lesion and extent of metastases
Tumor staging incorporates what 3 things?
1) Size of the primary tumor
2) The presence of lymph node spread
3) Distant metastases
What is TNM?
TNM
T (primary tumor): TX, T0, T1, T2, T3, T4
N (regional lymph nodes): NX, N0, N1, N2, N3
M (metastasis): Mx, M0, M1
True or false: Some cancers are grouped into five stages (0-IV)
True (0 = abnormal, 4 = metastasis)
Name a morphologic method for diagnosing cancer
Biopsy
The hallmark of a cancerous growth is what?
metastasis
