Tumour Precursors, Carcinogenesis And Genetic Changes

Question 1

Evidence of precursors of invasion and metastasis in organs

Answer 1

Architecture of epithelium changes

Changes in cytological morphology of cells

Question 2

intra-epithelial neoplasms

Answer 2

Pre-invasive stages in squamous epithelium

Normal -> low grade CIN -> high grade CIN -> cancer

Question 3

Cytological features of high-grade cervical intra-epithelial neoplasm

Answer 3

Abnormal nuclei, abnormal mitosis, loss of nuclear polarity, loss of differentiation

Question 4

Carcinogens

Answer 4

Agents which induce cancer in man or animals

Question 5

Carcinogenesis

Answer 5

process of cancer induction

Question 6

Types of carcinogen

Answer 6

Biological -> bacteria, viruses, parasites

Chemical -> natural synthetic

Physical -> UV or ionising radiation

Question 7

How to study mechanisms of carcinogens and cancer progession

Answer 7

Molecular genetic analysis of cancers and their precursor legions

Animal models

In vitro carcinogenesis and immortalisation

Inherited cancers in humans - susceptibility precursors

Question 8

Dose response

Answer 8

A linear relationship between the amount of carcinogen delivered in a single dose and the number of tumours which develop

Question 9

Latent period

Answer 9

Time lag between the administration of a carcinogen and appearance of macroscopic tumours

Higher dose=shorter lag time
Lower dose= extended lag time

Question 10

Threshold dose

Answer 10

The dose below which no tumours will form

Question 11

Stages in carcinogenesis

Answer 11

Initiation -> promotion -> progression

Question 12

Initiation

Answer 12

Alteration of normal cell into potentially cancerous cell -> caused by carcinogens acting as mutagens to cause irreversible mutations

Question 13

Promotion

Answer 13

A process which permits clonal amplification of the initiated cell
Promoters do not act as mutagens -> they only induce proliferation

Question 14

Progression

Answer 14

Acquisition of further mutations within the neoplasticism clone drive progression to a malignant neoplasm

Question 15

Replicative sensescence

Answer 15

Primary cells undergo a defined number of cell divisions -> after this the cells enter cell cycle arrest and are held in G0 -> eventually dying by apoptosis

Question 16

Hayflick number

Answer 16

The defined number of cell divisions a primary cell will undergo - approx 50-70

Question 17

Telomeres

Answer 17

Repetitive sequences (TTAGGG) at the end of chromosomes -> which form loops to protect the chromosome end from eroding away during replication

Question 18

Telomerase

Answer 18

Enzyme found in stem cells which maintains telomere length

Question 19

Retinoblastoma

Answer 19

Both inherited (1 mutation pre-zygotic, 1 mutation post zygotic) and sporadic (both mutation occur post zygotic)

Question 20

Syndromes in which heterozygous express the tumour phenotypes

Answer 20

The affected individual has genotype regular/mutant

• > autosomal dominant inheritance
• > inherit 1st mutation -> acquire 2nd mutation -> resulting genotype favours mutant

Question 21

Syndromes in which homozygous have increased risk of cancer

Answer 21

Affected individual has genotype mutant/mutant

Homozygous for mutant gene

Inheriting 2 mutant alleles - one from each parent

Question 22

What do studies of inherited cancer tell us

Answer 22

Cancer is a multi stage process

Maintaining error free DNA is crucial

Control restricting cellular lifespan must overcome for tumour progression

More than one mutation nis necessary for progression

Cancer is a genetic disease -> the initiating event is a somatic mutation in a single cell