CANCER

and
CANCER GENETICS
Concept: Oncogene, protooncogene, tumerogenic virus,
provirsus and distinguish between v-src and c-src.
Structure and function of various sarcoma virus,
structure and function of SV 40 and polyoma virus,
Philadelphia chromosome
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 CANCER
The term cancer is derived from Latin
Cancrum the actual medical term for
cancer is neoplasia.
Cancer is variously known as malignant
tumor, neoplasm (new growth) or
neoplastic tumor.
The initiation of tumor in an organism is
called oncogenesis (oncos, mass or
bulk; genesis birth) and therefore the
study of cancer is called oncology.
 Definition
Cancer is an abnormal growth of cells
caused by multiple changes in gene
expression leading to dysregulated
balance of cell proliferation and cell
death and ultimately evolving into a
population of cells that can invade
tissues and metastasize to distant sites,
causing significant morbidity and, if
untreated, death of the host.
 CANCER TERMINOLOGY
Classification by the site of origin of the tumour:
Breast: carcinoma of ductal, medullary, papillary, etc. ce lls
Lung: small cell, bronchioloalveolar, squamous, large cell
carcinomas
Bone: osteosarcoma, Ewing's sarcoma
Eye: retinoblastoma
Lip, tongue, mouth, nasal cavity: squamous cell carcinoma
Lymphocytes: acute lymphocytic leukaemia, chronic lymphocytic
leukaemia, Hodgkin's lymphoma
Ovary: adenocarcinoma, choriocarcinoma, teratoma, Brenner
tumour
Testis: seminoma, teratocarcinoma,
 CANCER TERMINOLOGY
Benign tumours
are generally slow growing and enclosed in a fibrous capsule
are relatively innocuous, although their location can make them
serious (such as a tumour located in the brain)
are not considered cancerous (that is, they are not malignant)
are given names that usually end in "oma" (although a melanoma is a
malignant skin cancer)

Malignant tumours
proliferate rapidly, invading neighbouring tissues
can metastasise, or spread, to other sites of the body
are named using the conventions of tissue, cell type, and origin
e.g. A tumour of the bone is an osteoma if benign and an osteosarcoma if malignant
 CANCER TERMINOLOGY
Classification by tissue type: Classification by the type of
cells:
carcinoma
epithelial cell Adenomatous cells
90% of all tumours ductal or glandular cells
derived from ectoderm (mostly) or
endoderm (some)
Squamous cells
sarcoma flat cells
connective tissue
2% of all tumours
derived from mesoderm Myeloid
blood cell
leukaemia
circulatory or lymphatic Lymphoid
8% of all tumours
lymphocytes or macrophages
derived from mesoderm
 PROPERTIES OF CANCER CELLS
(1) Decreased Density-dependent inhibition of Growth
(2) Loss of adhesiveness
(3) Morphological and cytoskeletal differences
(4) Loss of Anchorage Dependence
(5) Loss of Contact inhibition
(6) Highly invasive
(7) Reduced requirement of extracellular growth
factors/lower serum requirements
(8) Angiogenesis
(9) Fails to differentiate normally
(10) Immortality of Transformed Cells in Culture
(11) Resistance to Apoptosis
(12) Other Biochemical properties
NORMAL CELLS VERSUS CANCER CELLS
Figure - A
possible five-hit
scenario for
colorectal
cancer, showing
the mutational
events that
correlate
with each step in
the adenoma
carcinoma
sequence.
G PROTEINS E.G. RAS
Figure 14. Transformation arrests
the differentiation of many
hematopoietic cell types.
(A) Morphology of erythroid cells
transformed by a temperature-
sensitive mutant of AEV at the
permissive (left) and nonpermissive
(right) temperatures. Note the high
frequency of blastoid cells at
permissive temperature and more
differentiated erythroid cells at
nonpermissive temperature.
(B) Morphology of temperature-
sensitive AMV-transformed myeloid
cells at the permissive and
nonpermissive temperatures. Note
the high frequency of immature
myeloid cells at permissive
temperature and of differentiated
vacuolated cells at nonpermissive
temperature. (Photographs courtesy
of H. Beug.)
Figure 13. Extensive myeloid proliferation occurs in AMV-infected
chickens. (A) Peripheral blood from a normal chicken. Note the
predominance of nucleated red blood cells. (B) Peripheral blood from a
chicken with AMV-induced myeloblastosis, characterized by the
presence of large numbers of immature myeloid cells, many of which
are in various stages of mitosis. (Photographs courtesy of M. Baluda
and J. Lipsick.)
Figure 13. Extensive myeloid proliferation occurs in AMV-infected
chickens. (A) Peripheral blood from a normal chicken. Note the
predominance of nucleated red blood cells. (B) Peripheral blood from a
chicken with AMV-induced myeloblastosis, characterized by the
presence of large numbers of immature myeloid cells, many of which
are in various stages of mitosis. (Photographs courtesy of M. Baluda
and J. Lipsick.)
The environment and CANCER
Some environmental agents associated
with cancer are:
Viruses
Tobacco smoke
Food
Radiation
Chemicals
Pollution
 VIRUSES
Virusesmostly in the form of DNA
viruseshave been causally linked to cancer.
human papillomavirusesprimarily types 16 and 18, which
are sexually transmittedhave been linked to cervical
cancer;
more than 25 other types of papillomaviruses have been
linked to cancer as well
hepatitis B and Clinked to cancer of the liver
human immunodeficiency virus (HIV)linked to Kaposi's
sarcoma and lymphoma
retroviruseslinked to cancers in animals other than
humans
 TOBACCO SMOKE

is associated with 50% to 60% of all cancer

deaths
is causally linked to cancers of the lung,
upper respiratory tract, oesophagus, bladder,
pancreas
is probably a cause of cancer of the stomach,
liver, kidneys, colon, and rectum
 FOOD
is connected to 50% to 60% of cancer
deaths
is causally linked to cancers of the lung,
upper respiratory tract, oesophagus,
bladder, pancreas
is probably a cause of cancers of the
stomach, liver, kidneys, colon, and rectum
 RADIATION
UV-B from the sun can damage DNA and is associated with
more than 90% of skin cancers, including melanomas
radon has been associated with lung cancer among those
who work in mines; general levels of radon have not posed
a significant cancer threat
electric and magnetic fields from power lines and household
appliances have not been demonstrated contributors to the
incidence of cancer or leukaemia
radio frequency electromagnetic radiation from mobile
phones or microwave ovens has not been linked to cancer.
nuclear radiation is of sufficient energy to ionise molecules
and is therefore carcinogenic.
 CHEMICALS
Chemicals, many of which have been historically linked
to the workplace, have been successfully limited through
public health efforts, because they have been associated
with a variety of cancers. Examples of common chemicals
that fall in this category are:

benzene benzo()-pyrene (myelogenous leukaemia)

arsenic containing pesticides (lung cancer)
polychlorinated biphenyls (liver and skin cancers)
mineral oils (skin cancer)
mineral fibres (lung cancer and mesothelioma)
WHO CAN DEVELOPED CANCER

Oncogenes
Growth factors
Growth factor receptors
Intracellular receptors
G-proteins
Tyrosine kinases

Transcription factors
Tumour suppressor genes
CARCINOGENS
CARCINOGENS
 POLLUTION
Pollution has been difficult to document
as a contributor to human cancer.

However, long-term exposure to high

levels of air pollution may increase lung
cancer risk by as much as 25%.

The fungal toxin aflatoxin B1 ( a potent

liver carcinogen produced by some molds
CARCINOGENS
CARCINOGENS
CARCINOGENS
CARCINOGENS
CHROMOSOMAL MUTATIONS
Single chromosome abnormalities
 TUMOUR SUPPRESSOR GENES
A tumor suppressor gene, or anti-oncogene, is a
gene that protects a cell from one step on the path to
cancer. When this gene is mutated to cause a loss or
reduction in its function, the cell can progress to
cancer, usually in combination with other genetic
changes.
RB - the retinoblastoma gene
Familial retinoblastoma
Sporadic retinoblastoma
p53
p16INK4a
Loss Of Heterozygosity (LOH)
Human Papilloma Virus (HPV)
CD4
CHROMOSOMAL MECHANISMS OF ONCOGENE ACTIVATION
CHROMOSOMAL MECHANISMS OF ONCOGENE ACTIVATION
Figure 6.7 Diagram showing the EWS protein, the FLI-1 protein, and fusion proteins
generated by translocations in Ewings sarcoma and other
soft tissue tumours. Domains are shown as follows: RNA-BD: RNA-binding domain,
ETS: ETS domain, LZ: leucine zipper, ZnF: Zinc finger.
GROWTH FACTOR RECEPTOR E.G. TYROSINE KINASE
RECEPTORS GROWTH FACTOR RECEPTOR E.G. TYROSINE
KINASE RECEPTORS
G PROTEINS E.G. RAS
Types of genes which may mutate
to cause cancer:

Tumour suppressor genes

Oncogenes
DNA repair genes
Telomerase
p53
CHROMOSOMAL MECHANISMS OF ONCOGENE ACTIVATION
CHROMOSOMAL MECHANISMS OF ONCOGENE ACTIVATION
CHROMOSOMAL MECHANISMS OF ONCOGENE ACTIVATION
CHROMOSOMAL MECHANISMS OF ONCOGENE ACTIVATION
 CHROMOSOMAL MECHANISMS OF ONCOGENE ACTIVATION

Activation of the MYC gene by juxtaposition with sequences from the IgH gene in
Burkitts lymphoma and B-cell ALL
p53
suppresses progression through the cell
cycle in response to DNA damage initiates
apoptosis if the damage to the cell is severe
acts as a tumour suppressor is a
transcription factor and once activated, it
represses transcription of one set of genes
(several of which are involved in stimulating
cell growth) while stimulating expression of
other genes involved in cell cycle control
Retinoblastoma (RB)
Retinoblastoma (RB) is a malignant tumor of the
developing retina that occurs in children, usually before
the age of five years.
All forms of retinoblastoma represent a mutation in the
gene RB1 located in in the region 13q14.1-q14.2.
The gene is about 180 kb in length with 27 exons that
code for a transcript of only 4.7 kb.
individual mutations are heterogeneous: 20% are
deletions larger than 1kb; 30% are small deletions or
insertions; 45% are point mutations.
mutations have been found in 25 of the 27 coding exons
and in promoter elements.