WK14: Molecular Oncology Flashcards
6 Hallmarks of Cancer
- Self-sufficiency in growth signals
- Insensitivity in anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
- Evading apoptosis
Cancer characteristics
- Clonality
- Autonomy
- Anaplasia
- Metastasis
In clonality genetic disease is at the _______ level
cellular (mutations have a critical role)
A proliferating mass of cells lead to ______ formation
tumor
What consequence of genetic instability is associated with mutations in offspring
Phenotypic Heterogeneity
Promote/ Accelerate cell proliferation
oncogenes
only 1 of a pair of oncogenes needed to be activated for it to express _____ _______
malignancy potential (dominant and highly conserved)
off state of oncogene
proto-oncogene
Inhibit growth and multiplication of mutated cells
TS (tumor suppressor genes)
True or False:
TS genes are dominant and highly conserved
False (recessive)
Cell adhesion molecules
APC, DCC
Regulators of cell cycle
RB1, Tp53
Matching Type:
1st HIT
2nd HIT
a. Gross chromosomal loss
b. TS mutation or inherited mutation
1st HIT - b
2nd HIT - a
Gene involved in sporadic mutation
Wild-Type TS Gene
Familial type of TS gene defects
Heritable Cancer Syndromes
True or False:
In Heritable Cancer Syndromes, there is a tendency to develop malignancy at an earlier age compared to wild-type mutations because 1st hit is already present at birth
True
Ensures fidelity of replication
DNA repair genes
increased propensity of oncogenes and TS genes to undergo mutation is called ________
Microsatellite Instability/MIN
areas of unstable DNA because mutations are already present there
MIN
Inhibits cell cycle progression & permits DNA repair to take place
P21
most common genetic alteration found in human cancer
P53
True or False:
anti-apoptotic = favors continuous proliferation of tumor cells
True
main mechanism of lymphoid tumors is overexpression of _____
BCL-2
Component of mitochondria released in response to apoptotic signals
Cytochrome C
Activates cascade resulting in DNA fragmentation and apoptosis
Executioner/Effector Caspases
two types of caspases
Initiator Caspases
Executioner/Effector Caspases
Prevent recombination and shortening of the lagging strand
telomeres
The telomere is a bio/repro clock which regulate amount of ______ in a cell
replications
Adds 6 nucleotide repeats to 3’-OH end of DNA
telomerase
Commonly used to define DNA sequence changes that alter protein function
Mutations
Occur in non-germline tissues
somatic mutation
____ _____ are heritable – causes cancer family syndrome and Mendelian cancer syndrome
Germline mutation
True or False:
In germline mutation, all cells are affected in offspring; risk is present at birth
True
Approximately _____% of breast, ovarian, and colon cancers are linked to hereditary risks
5-10%
Clinical features of Hereditary Cancer Syndrome
- 2 or more relatives in a family is diagnosed with cancer
- > 1 gen is affected
- 1 or more types of clustering of specific tumor types are present
Common in tissues with rapid turnover
Autonomy
mean length of time for division of all tumor cells present
doubling time
True or False
The growth of cancer is directly proportional to rate of progression and aggressiveness of tumor
True
LOW number of cells, circulating factors, and nutrients in the tumor bed
Lag Phase
Rapid proliferation phase
Log Phase
Tumors in the _______ phase tend to be resistant to
chemotherapy and radiotherapy
plateau
earliest time for cancer to be clinically detected
Junction between lag and log phases
Only phase of the cell cycle that is susceptible to manipulation by external agents
S-phase
if promoted by cyclin → cell goes into mitosis
Junction between G2 and M
commonly affected in many malignancies
Junction between G1 and S
Therapeutic goal in this phase: is the prevention of mitosis in the presence of damaged DNA
G2/M checkpoint
Area most often involved in cancer
G1/S checkpoint
Phosphorylation of Rb gene results in:
Activation of several genes needed for S phase progression
Promotes differentiation through association with
transcription factors
caused by Rb gene mutation
Retinoblastoma
True or False:
The more poorly differentiated the tumor is, the more anaplastic it tends to be, the
more aggressive the behavior of the tumor is
true
Continued proliferation results in mass formation
anaplasia
lifestyle related causes of malignancy
Tobacco, Diet , Sexual practices
The most carcinogenic substance ever produced by human
beings for commercial consumption
Tobacco
2nd most common carcinogenic substance produced by human beings for commercial consumption
Alcohol
The higher the caloric intake, the higher intake of red meat = the higher the chance of developing ______
colon cancer
The use of _______ in post-menopausal women to alleviate the post-menopausal symptoms can increase the development of breast cancer
estrogens
Ionizing radiation includes: ______ ____ and _______ ______
electromagnetic rays & particulate matter
Exposure to radiation from sunlight can cause a high risk of ____ _____ and ______
skin cancer and melanoma
Most RNA oncogenic viruses belong to the family of retroviruses that contain ______ _____
reverse transcriptase
Many patients with gastric cancers have history of ________
chronic peptic ulcer disease
_____ and tissue cytology usually for masses that are hard to access like lung and liver masses
FNAB
Useful for identifying the primary site of tumor if the patient already presents with metastasis
Cytokeratin phenotyping
_____ is diagnostic for non-seminomatous germ cell tumors
AFP
Can provide baseline information In staging, certain blood examinations are necessary such as functional assessment of end organs
Serum chemistries
main site of activation and deactivation of chemotherapeutic agents
Liver function test
______ insufficiency can lead to prolonged activation or prolonged deactivation which leads to toxicity
Hepatic
