67. Definition of tumor (oncogenesis, tumorsuppressor genes)

Question 1

Definition of tumor

Answer 1

pathologic lesion with IRREVERSIBLE genetic damage in the background -> abnormal cell proliferation

Question 2

Neoplasia - ?

Answer 2

new tissue proliferation

Question 3

Why we also call neoplasm tumor?

Answer 3

one of the main characteristics of inflammation (swelling). Tumor in Greek = “-oncos” -> oncology

Question 4

Immortalisation

Answer 4

Progressive growth of neoplastic cells , infinite proliferation ability. But neoplasm will have resting periods when it will stay in stable state and it won’t grow for a while

Question 5

Oncogenes - ?

Answer 5

A mutated form of a type of protooncogene, (which is involved in normal cell growth and division). Oncogenes are more active

Oncogenes are dominant (gain-of-function mutation in a single copy of the cancer-critical gene can drive a cell toward cancer)

Question 6

What is special about neoplasm metabolism (Warburg effect) ?

Answer 6

Anaerobe glycolysis instead of aerobic

Question 7

Can neoplasm apoptose?

Answer 7

Usually neoplastic cells lose apoptic ability (no programmed death)

Question 8

What is special about neoplasm <-> blood vessels ?

Answer 8

Continuous angiogenesis

Question 9

Inflammatory proccesses <-> neoplasm

Answer 9

Inflammatory processes will actually SUSTAIN neoplasm

Question 10

General characteristics of carcinogenesis:

Answer 10

• immortalisation
• oncogenes / tumorsupressor genes
• anaerobic glycolysis > aerobic glycolysis
• loosing of apoptic ability
• continuous angiogenesis
• predisposition to tissue invasion and metastasis (malignant!)
• sustaining inflammatory processes
• genomic instability as predisposition factor

Question 11

Somatic vs germinal mutation ?

Answer 11

Somatic - mutation in somatic cell
Germinal - mutation in a gamete during gametogenesis

Question 12

spontaneous vs induced mutations

Answer 12

Spontaneous - error in DNA replication
Induced - environmental/epigenetic effect

Epigenetics - the study of changes in organisms caused by modification of gene EXPRESSION rather than alteration of the genetic code itself

Question 13

Classification of mutations depending on amount of affected genes:

Answer 13

• gene mutation / pointmutation - 1 gene
• chromosome mutation - > 1 gene
• genome mutation - whole genome is affected

Question 14

Do mutation always lead to carcinogenesis?

Answer 14

NO!
- apoptosis.
- enzyme can repair the error.
- error can occur in functionally inactive location.
- error can occur in a neutral location regarding to oncogenesis (may be alteration in function but won’t cause carcinogenesis)

Question 15

What are requirements for start of carcinogenesis ?

Answer 15

• numerous genetic mutations (in functionally active locations)
• preservation of replication ability (transmission of genetic mutation to daughter cells, telomerase activity)

Question 16

genetic instability

Answer 16

Mutation leads to more mutations

Question 17

How do neoplastic cells maintain their proliferation ability ?

Answer 17

Reactivation of telomerase enzyme -> immortalization

Question 18

How does telomerase function in normal cells ?

Answer 18

Every time cells divide, their telomeres shorten, which eventually prompts them to stop dividing and die. Telomerase prevents this decline in some kinds of cells, including stem cells, by lengthening telomeres (adding TTAGGG to 3’ end)

As cell loses its ability to proliferate (adult cell), it will lose the activity of telomerase, so chromosome will be shorter during every DNA replication, shorter chromosome - older the cell (senescence = cell aging)

Question 19

Senescence - ?

Answer 19

aging

Question 20

Main targets of carcinogenesis:

Answer 20

• protooncogenes =normal genes producing metabolites to help cell to proliferate
• oncogenes = mutant or highly expressed variants of protooncogenes. Have autonomous function, don’t need normal growth signals
• suppressor genes = inhibit cell proliferation through regulation of cell cycle
• stability genes = part of DNA repair mechanisms

Question 21

Protooncogenes

Answer 21

Normal genes helping cell to proliferate
- growth factors (epidermal GF (EGF), platelets derived GF (PDGF), TGF, and more…)
- nuclear factor receptors
- signal molecules
- transcription factors

Question 22

Tumorsuppressor genes

Answer 22

Normally inhibiting activity of proliferation of the cell
In neoplastic processes usually are inactivated (genetic mutation). These mutations are recessive (except p53) -> both alleles need to be mutated to a phenotypic manifestation

Question 23

Stability genes

Answer 23

members of DNA repair system, maintain genomic integrity
- keep genetic variance low
- indirect tumorsuppressors
- due to stability genes mutations and inactivation, mutations rate increases in other cells
-