Tumor pathology 5 MW + Flashcards Preview

ME2308 Principles of Disease > Tumor pathology 5 MW + > Flashcards

Flashcards in Tumor pathology 5 MW + Deck (13)
Loading flashcards...
1

Disruption of normal regulatory genes

–Tumour-suppressor genes (anti-oncogenes)

•Normal growth-inhibiting genes

–Genes negatively regulating mitosis - Rb

–Genes regulating APOPTOSIS

–Genes regulating DNA repair

–PROTO-ONCOGENES

•Normal genes that promote normal cell growth and mitosis

 

2

What is the key event in tumour formation

Uncontrolled cell proliferation via cell cycle dysregulation through loss of tumour suppressor gene function

3

Retinoblastoma gene: an anti-oncogene

Rb gene mutations favour cell proliferation

•Mutations in other genes controlling pRb phosphorylation mimic the effect of pRb loss:

–Mutational activation of cyclin D or CDK4

–Mutational inactivation of CDKIs also drive proliferation

 

Note: Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissueof the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively found in young children.[1]

4

                        Sporadic vs inherited retinoblastomas

•“TWO-HIT HYPOTHESIS” of oncogenesis

–INHERITED FORM

•one defective inherited copy of pRb

•somatic point mutation of other copy

–SPORADIC FORM

•both hits occur in a single cell

loss/inactivation of both normal

allelic copies gives rise to cancer

5

Carcinogenesis

•Heredity

–accounts for 5-10% of all cancers

–Inherited cancer syndromes

–Familial cancers

Autosomal recessive syndromes of defective DNA repair

Note: An autosomal recessive disorder means 2 copies of an abnormal gene must be present in order for the disease or trait to develop.

6

Inherited predisposition to cancer

Familial cancers

•family clustering of cancers but individual predisposition unclear

multifactorial inheritance

•early age of onset

•multiple / bilateral tumours

-Some Breast cancers

-Some Ovarian cancers

-Non-FAP colon cancers

 

7

Proto-oncogenes

•Normal genes coding for normal proteins that regulate growth

Growth factors

–Growth factor receptors

–Signal transduction

8

ONCOGENES
Cancer-causing genes
 

•   Derived from proto-oncogenes

Activated by:

• Alteration of proto-oncogene structure

• point mutation

• chromosome rearrangements + translocations

Dysregulation of proto-oncogene expression

• gene amplification

overexpression

9

Oncogenes generate active ONCOPROTEIN products e.g?

Growth Factors

–Growth Factor Receptors

–Proteins involved in Signal Transduction

–Nuclear Regulatory Proteins

–Cell Cycle Regulators

10

Viral carcinogenesis:
More than one mechanism

•virus genome inserts near a host proto-oncogene

•viral promoter or other transcription regulation elements cause proto-oncogene over-expression

Retroviruses  insert an oncogene into host DNA causing cell division

•DNA viruses known to cause cancer in humans

HPV (cervical cancer)

Hepatitis B (liver cancer)

EBV (Burkitt lymphoma)

11

Chemical carcinogenesis

Adduct formation at particular chromosome sites lead to activation of oncogenes and suppression of anti-oncogenes

 

12

Multistep caricnogenesis

•All sporadic cancers harbour multiple genetic aberrations (deviation from norm)

Abnormalities accumulate with time

•Activation of several oncogenes and loss of 2 or more anti-oncogenes occurs in most cancers

13

Diagram