MOLECULAR ONCOLOGY Flashcards by Queenie Mae

is the study of tumors.
A _ or _ , is a growth of tissue that exceeds that of normal tissue and is not coordinated with it.

Oncology
- tumor, or neoplasm

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is a term that includes all malignant tumors.

Cancer

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is the study of cancer at the molecular level, using techniques that allow the direct detection of ___, down to __.

Molecular oncology
- genetic alterations
- single-base-pair changes

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HALLMARKS OF CANCER

Self-sufficiency in growth signals Insensitivity in anti-growth signals Tissue invasion and metastasis Limitless replicative potential Sustained angiogenesis
Evading apoptosis

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CANCER GENE CHARACTERISTICS

Clonality
Autonomy
Anaplasia
Metastasis

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Each tumor, no matter how large or heterogenous, ultimately originated from a single transformed cell called the __ or__

CLONALITY
- cell of origin or mother cell

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is defined as two tumors deriving from the same progenitor cell that previously underwent malignant changes.

Clonality

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__ (derived from mother cell) will express the same genetic instability or malignant transformation.

Clonality
- Daughter cells

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TYPES OF CANCER GENES

Oncogenes
Tumor Suppressor Genes
DNA Repair Genes

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• Principal key player for the fast proliferation.
• Mutated proto-oncogene
• Promote or accelerate cell proliferation (normal cells: regulate cell growth).
• Represent the abnormal stimulation of a particular gene.

ONCOGENES

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Dominant in pattern
o Only 1 copy of gene inherited from parent gene, it can be readily
expressed in the offspring.
o When activated, their expression is dominant.
o Meaning, only 1 of a pair of oncogenes needed to be activated for it to express malignancy.
• In the normal population, the oncogene must always be in “__” state.
o Meaning, every individual has an oncogene but inactivated. - It is what we call ___ .
• __>____>___

Oncogene
- OFF
- proto-oncogene
- o Proto-onco >mutation > oncogene

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– encodes for a cell surface receptor that can stimulate cell division. It is amplified in up to 30% of __

HER-2/neu
- human breast cancers

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HER

human epidermal growth factor receptor

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Neu

neural tumor (from rodent)

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– involved in kinase signaling pathways that ultimately control transcription of __,__ and __ , associated with __.

RAS – Rat Sarcoma virus
- genes, regulating cell growth and
differentiation
- pancreatic cancer

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– enzyme in activating phosphorylation (activates gene for cell cycle) process.

Kinase

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is an activating mechanism especially for those associated with cell growth.

Phosphorylation

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– a transcription factor and controls expression of several genes, implicated with __

malignant transformation of cells in the bone marrow.

__ converts DNA to RNA to produce a protein with a malignant transformation.

o MYC – myelocytomatosis
- Burkitt lymphoma
- Transcription

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• Inhibit growth and multiplication of mutated cells; prevent further neoplastic transformation.
• Recessive in pattern.
o Needs two copies for full expression.
• Always in “ON” state in normal population.

TUMOR SUPPRESSOR (TS) GENES

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TYPES ACCORDING TO MODE OF ACTION

Cell Adhesion Molecule
Regulators of the Cell

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– Genes that can adhere to cell
membrane. Examples:
1
2

• Cell Adhesion Molecule
-APC – Adenomatous Polyposis Coli - DCC – Deleted in Colon Cancer

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– involved in the inhibition of cell
cycle. Examples:

Regulators of the Cell
- Retinoblastoma RB1
- TP – Tumor Protein Tp53 (p53)

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• Hypothesis on the formation of malignancies.
- A normal cell must undergo transformation in order to become __ .
• 1st hit – __
> Inhibition of cell cycle
• 2nd hit – —-
> Derangement in the chromosomal level

KUDSON’S TWO-HIT HYPOTHESIS
- malignant
- TS gene mutation or inherited mutation
- gross chromosomal loss

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TYPES OF tumor supressor GENE DEFECTS

Wild-Type Tumor Supressor gene
2 Heritable cancer syndromes

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– occurs in the natural state; sporadic mutation. o 1st hit – ____ o 2nd hit – ___

Wild-Type TS gene - mutation in 1 of the chromosome pair; predisposition - damage or deletion of normal TS gene in the other pair

o Familial type o Germline mutation o 1st hit: __ o 2nd hit: __ o Tendency to develop ___ at an earlier age

Heritable cancer syndromes - inherited mutation - damage/deletion of normal TS gene in the other pair - malignancy

* Ensures reliability of replication * Checks and corrects mismatched pairs * Example 1 2

DNA REPAIR GENES - BRCA1 - BRCA2

• If non-functional: o Mutation → inefficient repair and replication → increased propensity of oncogenes and TS genes to undergo mutation → __

BRCA – BReast CAncer - Microsatellite Instability/MIN

areas of unstable DNA caused by mutations present in the location.

Microsatellite Instability/MIN

Gain of function -> CANCER Promote cell proliferation ex:

Oncogene Her2 Neu Ras Myc

loss of function-> CANCER Inhibit growth and multiplication of mutated cells ex

Tumor Supressor gene - TP53, Rb, APC, DCC

Loss of function-> CANCER Checks and corrects mismatched pairs ex

DNA Repair BRCA1 and BRCA2

CYCLINS • Acts as activator

o Cyclin D – G1 cyclin o Cyclin E – G1/S cyclin o Cyclins E & A – S-phase cyclins o Cyclin B – M-phase cyclin

• Cyclins need to turn on Cyclin Dependent Kinase (CDK)

o Cyclin D – CDK4, CDK5 o Cyclin E – CDK2 o CyclinsE&A–CDK2 o Cyclin B – Cdc2 (CDK1) § Cyclin B/Cdc2 is called Mitosis Promoting Factor (MPF).

G2 checkpoint for:

Cell size dna replication

Spindle Assembly checkpoint for

chromosome attachment to spindle

G1 checkpoint for

cell size nutrients growth factor dna damage

resting state

dna replication enzymes are activated

S phase

• Cyclin regulators are __ >halts cell cycle progression to facilitate DNA repair, if damage is repairable (reactivation of capping of the DNA) > activates apoptosis in cases of severe DNA damage.

cell cycle inhibitors (CDKi)

• Most commonly seen genetic defect in cancer • Example:

1. p21 – 2. RB – 3. p53 –

– inhibits cell cycle progression

p21

– keeps the entire replication in check (mutation seen in ___)

RB Retinoblastoma

– “guardian of the genome”. Plays an important role in cell cycle checkpoints

p53

• Programmed cell death • As cells grow older, their tendency to develop mutations gets higher, thus it is necessary to prevent continuous proliferation of cells. • Markers:

APOPTOSIS - Cyclin Regulators (p53 protein.

COMPONENTS OF APOPTOTIC PATHWAY ___- Pivotal decisional checkpoint

BCL-2 family of proteins

• Programmed cell death • As cells grow older, their tendency to develop mutations gets higher, thus it is necessary to prevent continuous proliferation of cells. • Markers:

APOPTOSIS - Cyclin Regulators (p53 protein.

Anti apoptosis

BCL-2 ( B-Cell Lymphoma) BCL- xL

PRO- Apoptosis

BAX BAD BAK BID

• Component of mitochondria released in response to apoptotic signals. • Increased Apoptotic signals → Cytochrome C stimulated → Activates cells that destroy the cell REFERENCE

CYTOCHROME C

CASPASES • 2 types:

Cysteine-containing ASPartate-specific ProteASES - Initiator Caspases - Executioner/Effector Caspases

– activated in response to apoptotic signal

Initiator Caspases

– activates cascade resulting in DNA fragmentation and apoptosis.

Executioner/Effector Caspases

• Cancer cells can grow without the presence of stimulators. • Commonly seen in tissues with rapid growth or turnover. ● Example: 1 2

AUTONOMY 1) Tissues exposed to environmental agents. > Epidermal or lining epithelial tissues o Suffix: CARCINOMA – malignancy of epithelial tissue. 2) Tissues whose proliferation is hormone dependent. o Breast, prostate.

● Commonly used to define DNA sequence changes that alter protein function. ● Change in the normal base-pair sequence. ● Two (2) types:

MUTATION 1) GERMLINE MUTATIONS 2) SOMATIC MUTATIONS

- change occurs during DNA replication before meiosis - Every cell in the body is affected - Can be transmitted to the next generation of individuals - Heritable ( Familial mendelian Pattern) - Early onset of dse

Germline mutation

- change occurs during DNA replication before mitosis - occurs in cell that divides often - pass to the next generation of cells not indi - Non- Heritable ( sporadic Pattern) - late onset of dse

somatic mutation

CARCINOGENS Classifications

• Occupation related causes • Lifestyle related causes: Tobacco, Alcohol, Sexual Practices, Diet • Ionizing radiation • Infectious carcinogens: Viral, Bacterial origin

• A known cause of cancer • Amount of smoking is __ to the development of cancer • Associated cancers are where the smoke passes through à __,__ and __

LIFESTYLE-RELATED : TOBACCO - DIRECTLY PROPORTIONAL - Lungs, Oral Cavity, and Nasopharynx

• 2nd most common carcinogenic substance produced by human beings • Associated with __ and _

ALCOHOL - liver cirrhosis and potential liver cancer

SEXUAL PRACTICES

• Sexual promiscuity • Multiple partners • Unsafe sex • Associated with Human Papillomavirus (HPV) which causes CERVICAL cancer

are classified into RNA and DNA viruses o ___ has a higher rate of cancer

• Viral carcinogens - RNA viruses

• Most RNA oncogenic viruses belong to the family of __ that contain __ → Mediates transfer of viral RNA into virus specific DNA

retroviruses reverse transcriptase

• Only bacteria implicated with cancer • Creates ulcers in GIT • Ulcerated areas are associated with continuous proliferation and repair

BACTERIAL: Helicobacter pylori

• Chronic repair/proliferation process can eventually get out of hand and give rise to malignancy • Many patients with gastric cancers have history of chronic peptic ulcer disease • Common ulcer sites: __,__,__

BACTERIAL: Helicobacter pylori - Esophagus, Stomach, Duodenum

DIET-RELATED RISKS • _ are derived from __ They came from nuts and grains which can lead to liver cancer

Mycotoxins Aspergillus spp.

• Includes electromagnetic rays and particulate matter • Mechanism: ↑ Free radical & mutations • Pathology (According to frequency):

IONIZING RADIATION 1. Leukemia 2. Thyroid Cancer 3. Lung and Breast Cancer • Radio Resistant Tissues: Bone, Skin and the GIT

NINE WARNING SIGNS MNEMONICS: CAUTION US

1. Change in bowel or bladder habits 2. A sore that does not heal 3. Unusual bleeding or discharge 4. Thickening of a lump in breast or elsewhere 5. Indigestion or difficulty in swallowing – progressive 6. Obvious change in a wart or mole 7. Nagging cough or hoarseness 8. Unexplained anemia 9. Sudden, unexplained weight loss – Most common

DIAGNOSIS OF CANCER • Definitive diagnosis by pathological examination • Pathologic examination may be done by __ • Specimen collection can be through 1 2 3

- Biopsy - endoscopy or surgical biopsy or FNAB (Cytology) o FNAB – Fine Needle Aspiration Biopsy

- Mining, pesticide workers

Arsenic - Lung, skin, liver

- Construction workers

Asbestos - Lung, mesothelioma

- Petroleum, rubber, chemical workers

Benzene Leukemia

- Metal workeds, electroplaters

Chromium Lung

- Shoe manufacturing

Leather dust - Nasal, bladder

- Chemical, dye, rubber workers

Naphthylamine Bladder

- Underground mining

Radon - Lung

- Coal, gas, petroleum workers

Soots, tars, oil - Lung, skin, liver

- Rubber workers, polyvinyl chloride manufacturing

Vinyl chloride Liver

- Furniture manufacturing

Wood dust - Nasal

MOLECULAR ONCOLOGY Flashcards

(79 cards)