Cancer arises due to genetic aberrations that accumulate in somatic cells and alter gene expression. There are several types of genomic changes including mutations, chromosome defects, and changes to oncogenes and tumor suppressor genes. Genetic testing can identify inherited cancer risk genes and guide diagnosis and treatment, while gene therapy holds promise for directly treating cancer at the genetic level.

1. Cancer
Genetics

2. Overview
• Brief introduction
• Understand the principles of the Hallmarks of Cancer
• Discuss the types of genomic changes that occur during
cancer development
• Understand the roles of oncogenes and tumor suppressor
genes
• Identify the uses of genomics in cancer diagnosis and
treatment
• New directions- genetic testing, gene therapy

3. What is Genetics?
• Is a study of heredity.
• Genes are basic unit of heredity.
• Genes- are the fractions or part of DNA molecule
which regarded as the genetic material.
• DNA(deoxyribonucleic acid) is a double
stranded molecule that is twisted into
helix.
• Each strand has sugar phosphate back
and Bases.
• Bases- Pyrimidine and Purine.
• Pyrimidines- Cytosine “C”, Thymine “T”.
• Purines- Adenine “A”, Guanine “G”.

4. DNA has -
Nucleoside and Nucleotide
• The base-pairing rules show how
nucleotides always pair up in
DNA.
Nucleotides always pair in the same way.
-A pairs with T
- C pairs with G
• A codon is a sequence of
three nucleotides that codes
for an amino acid.
• The genetic code matches each
codon to its amino acid or
function.

5. Gene Expression
• It is a multi step process which involves
• Replication- is a process in which DNA copies itself
to produce identical daughter molecules of DNA.
• Transcription- process through which a genetic
information transfer from DNA to RNA.
• Translation – protein synthesis

6. • At the cellular level,cancer is a disease of the genome
• Cancer arises from the accumulation of genetic
aberrations in somatic cells
• These aberrations consist of mutations and chromosome
defects
• Together, they lead to altered gene expression
• Over 500 genes are now known to be involved in cancer
development.

7. Understand the principles of the
Hallmarks of Cancer
Cancer
• A disease of extraordinary diversity and complexity
• But - disparate malignancies share fundamental qualities
• The complexity merely reflects different solutions to the
same challenge:
Cancer cells must overcome multiple barriers used by
the organism to prevent expansive cell proliferation

9. Genetic aberrations give rise to the
hallmarks of cancer
•If we know which genes are involved, we
can:
Have a better understanding of cancer biology
Develop diagnostic and prognostic markers
Follow the clinical course
Develop targeted treatment

10. 2. Types of genomic changes that occur
during cancer development

12. Mutation
• The basic mechanism in all cancer is mutation. Mutation is change
in DNA sequence.
• Rate in humans ~5x10-9 /nucleotide / generation = 25
mutation/cell/generation
• Carcinogenic agents are involved through causing mutation. It may
be-
 Germline mutations are responsible for 5% to 10% of cancer
cases. This is also called familial cancer. These mutations are
present in every cell of the body and are passed from parent to
child.
 Sporadic cancer or somatic mutation are caused by tobacco,
over-exposure to UV radiation, and other toxins and chemicals.
These mutations are not in every cell of the body and are not
passed from parent to child.

13. Types of gene Mutation
I. Point mutations
II. Substitutions
III. Insertions
IV. Deletions
V. Frameshift

14. Chromosome aberrations

16. Genes & cancer
•Four classes of normal regulatory genes are
the principle target of genetic damage.
1. -The growth promoting Proto-oncogenes
2. -The growth inhibiting tumor suppressor
genes
3. -Genes that regulate programmed cell
death(Apoptosis)
4. - DNA repair genes

17. Proto-oncogene
• Have multiple roles, participating in cellular functions related
to growth & proliferation.
• Proteins encoded may function as growth factors or their
receptors, signal transducers, transcription factors or cell
cycle components.
• Mutations convert proto-oncogene into constitutively active
cellular oncogene that are involved in tumor development.
Types of Proto-oncogenes:
1)Cellular oncogenes(c- oncogenes): proto-oncogene
which have been to mutate in any individual.
2)Normal oncogene(n-oncogene): proto-oncogenes that
have not been found to mutate.

18. Activation of proto-oncogene

20. Oncogene
• First identified in transforming retroviruses
• Act by gain of function
• Dominant (activation of one allele sufficient)
Activated by
a) mutation
b) chromosome translocation
c) gene amplification
d) retroviral insertion

22. TUMOUR SUPPRESSOR GENES
• First identified for inherited Retinoblastoma and
Wilm’sTumour
• Act by loss of function
• Recessive (inactivation of both alleles necessary)
• Inactivated by
a) mutations
b) deletions
c) DNA methylation (epigenetic)
Cause predisposition to cancer

23. Tumor suppressor genes code for proteins that slow down cell
growth and division, the loss of such proteins allows a cell to grow
and divide in an uncontrolled fashion.

24. Tumor Suppressor Genes Act Like a
Brake Pedal

25. Tumor suppressor genes involved
in human neoplasm

26. DNA repair genes
• Each cell loses more than 10000 bases per day from
spontaneous breakdown of DNA at body temperature.
• Fortunately, the DNA repair genes code for enzymes
that fix crack in DNA.
• Genetics disorders in which DNA repair process is
defective exhibit risk for certain type of cancers-
- Xeroderma pigmentosa
- Ataxia telangiectasia.
- Bloom syndrome.
- Fanconi’s anaemia

27. • RB gene : Governor of the
cell cycle.
• p53 gene : Guardian of
genome.

30. Genetic testing
• Inherited cancer genes can significantly increase the
lifetime risk of developing cancer . Therefore, the
identification of well characterized germline cancer genes
can be used to predict both the type and extent of cancer
susceptibility.
• Testing is done on a small sample of body fluid or tissue—
usually blood, but sometimes saliva, cells from inside the
cheek, skin cells, or amniotic fluid.
i. A “positive test result” means that the laboratory found a
specific genetic alteration (or mutation) that is associated with a
hereditary cancer syndrome.
ii. A “negative test result” means that the laboratory did not find
the specific alteration that the test was designed to detect. this
result is most useful when working with a family in which the
specific, disease-causing genetic alteration is already known to
be present.

31.  When a person has a strong family history of cancer but
the family has not been found to have a known
mutation associated with a hereditary cancer
syndrome, a negative test result is classified as an
“uninformative negative”.
 If genetic testing shows a change that has not been
previously associated with cancer in other people, the
person’s test result may report “variant of unknown
significance,” or VUS.
 If the test reveals a genetic change that is common in
the general population among people without cancer,
the change is called a polymorphism.

34. Gene therapy
The basic concept of gene therapy is to introduce a gene
with the capacity to cure or prevent the progression of a
disease.
Three different gene therapy treatment approaches:
1) Immunotherapy uses genetically modified cells and viral particles to
stimulate the immune system to destroy cancer cells.
2) Oncolytic virotherapy, which uses viral particles that replicate
within the cancer cell to cause cell death, is an emerging treatment
modality that shows great promise, particularly with metastatic cancers.
3) Gene transfer is a new treatment modality that introduces new
genes into a cancerous cell or the surrounding tissue to cause cell
death or slow the growth of the cancer.

35. GENE TRANSFER
•Divided into-
• Somatic cell gene therapy
In vivo somatic gene therapy In vitro somatic gene therapy

36. Germ cell gene therapy
Stem cell therapy

37. Gene therapy approved by FDA

38. No genetic disorders have been
conclusively cured by gene therapy, but
some promising results are obtained from
ongoing clinical trials.

39.  Cancer is a genetic disorder in which the normal control
of cell growth is lost.
 The basic mechanism in all cancer is mutation, either in
the germ line or much more frequently, in somatic cells.
 Cancer is multi-factorial diseases, much remains to be
learned about the genetic processes of carcinogenesis
and about the environmental factors that alter DNA and
thus lead to malignancy.
Conclusion