Lecture 1+2

Question 1

Common event in solid cancers

Answer 1

Point mutations in Ras is a common event in many solid cancers

Question 2

What are Proto-oncogenes and their roles

Answer 2

Proto-oncogenes are normal cellular versions of oncogenes. Their protein products have diverse roles including growth factors, growth factor receptors, signalling proteins and nuclear proteins.

Question 3

where do carcinomas originate and give examples

Answer 3

Carcinomas (80 -90% cancers) are of epithelial origin and include cancers of the breast, colon, lung

Question 4

How is Burkitt’s lymphoma characterized

Answer 4

Burkitt’s lymphoma is characterized cytogenetically by t(8;14) translocations which involve the juxtaposition of the myc gene to the Ig heavy chain gene locus on chromosome 14.

Question 5

Do TSGs (tumour suppressor genes) restrain cell proliferation

Answer 5

Yes

Question 6

What TSG play’s key role in cell cycle regulation

Answer 6

Rb is a TSG which has a key role in cell cycle regulation

Question 7

What are oncogenes and their function

Answer 7

oncogenes are activated versions of proto-oncogenes and are often involved in deregulating cell division and growth

usually “gain of function mutations”
generally dominant eg cMYC

Oncogenes can become activated by
* genetic mutations
* chromosomal translocations
* gene amplification

Question 8

Tumor progression is…..

Answer 8

the tendency of tumor cells to develop from benign to malignant over time

Question 9

What are neoplasm/tumor

Answer 9

A tumor or Neoplasm is a group of cells which display unregulated proliferation

Question 10

Benign definition

Answer 10

• A Clustered of single mass ,
• not capable of indefinite growth
• not able to invade healthy surrounding tissue

Question 11

Malignant defintion

Answer 11

A tumour that continues to grow and becomes progressively more invasive

Question 12

What is Metastasis

Answer 12

Metastasis is the ability of a malignant tumor to form 2 (degree) tumors (metastases) at other sites in
the body.

Question 13

What is Metastatic potential

Answer 13

When small clusters of cancerous cells dislodge from the primary tumour to invade the blood or lymphatic vessels and are carried to distant sites, take up residence and continue to proliferate

Question 14

Where do sarcoma arise and give examples

Answer 14

Sarcoma (1% cancers) arise from a variety
of mesenchymal cell types including
osteoblasts (bone-forming
cell)[Osteosarcoma], adipocyte (fat
cell)[Liposarcoma] and fibroblast
(connective tissue cell)[Fibrosarcoma].

Question 15

Examples of non - epithelial cancers and where they originate

Answer 15

• Leukemia, Lymphoma and multiple
  myeloma (9% of all cancers) are
  malignant tumours of hematopoietic
  cells derived from bone marrow (cells
  of the immune system, including T and
  B cells
• arise from cells that form
  part of the central and peripheral
  nervous systems. Includes gliomas,
  glioblastomas, neuroblastomas,
  medulloblastomas. Makes up 1.3%
  of all diagnosed cancers,

Question 16

Tumor-suppressor genes

Answer 16

allow cancer cell survival when they fail
usually “loss of function mutations”
generally recessive eg Rb

Question 17

Apoptosis

Answer 17

when faults-leads to abnormal cell survival

Question 18

How does an oncogene cause cancer

Answer 18

An activating mutation in a single oncogene is not sufficient to cause cancer

Oncogenes must collaborate with one another and with inactivation of Tumour Suppressors in order to generate cancers

Question 19

Are tumors the result of a change in
DNA sequence

Answer 19

Usually,
- Broadly cancers arise due to Genetic (DNA sequence) (Carcinomas, Leukemia, Lymphomas)
- Epigenetic (Gene expression) alterations in 3 types of genes: Oncogenes, Tumour Suppressor Genes and Caretaker Genes (such as DNA repair genes)

Question 20

Are tumors derived from a single
abnormal cell?

Answer 20

Various observations suggest that this is the case:

1. Karyotyping/DNA Analysis - Karyotyping of cancer cells remains the gold standard since it provides a global analysis of the abnormalities in the entire genome of a single cell.
2. X Chromosome inactivation

Question 21

What is the cumulative damage model

Answer 21

For most tumors, it is the cumulative damage model that best fits the data (Cancer and Age-takes time for
malignant tumours to develop)

Tumors arise from a population of abnormal
cells, derived from a single mutant ancestor,
acted upon by mutation and selection

Question 22

What are some examples of Inherited single gene defects and their Cancer Susceptibility

Answer 22

Retinoblastoma - RB tumour suppressor (childhood eye cancer)

Li-Fraumeni syndrome - p53 (children and young adults develop different cancers including brain tumors, leukemia breast cancer.)

BRCA1 and 2-predisposition = breast and ovarian cancer.

APC (adenomatous polyposis coli) gene mutations = cause of inherited precancerous polyps, and a
contributor to colon cancer

Question 23

What is the difference between sporadic and familial retinoblastoma?

Answer 23

Familial (Hereditary): Multiple tumors, affecting both
eyes, early onset, 6x increased cancer risk

Sporadic (Non-hereditary): Single tumor,
affecting one eye, later onset

Question 24

What “causes” cancer?

Answer 24

It is multifactorial, a complex genetic basis with environmental triggers

Examples:
Smoking - Lung Cancer
Viruses and other infectious agents - HPV and cervical cancer
Obesity - Colon cancer
UV exposure - Melanoma (skin cancer)
Genetic Background - Li Fraumeni syndrome, retinoblastoma etc