Lecture 1+2 Flashcards
Common event in solid cancers
Point mutations in Ras is a common event in many solid cancers
What are Proto-oncogenes and their roles
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.
where do carcinomas originate and give examples
Carcinomas (80 -90% cancers) are of epithelial origin and include cancers of the breast, colon, lung
How is Burkitt’s lymphoma characterized
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.
Do TSGs (tumour suppressor genes) restrain cell proliferation
Yes
What TSG play’s key role in cell cycle regulation
Rb is a TSG which has a key role in cell cycle regulation
What are oncogenes and their function
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
Tumor progression is…..
the tendency of tumor cells to develop from benign to malignant over time
What are neoplasm/tumor
A tumor or Neoplasm is a group of cells which display unregulated proliferation
Benign definition
- A Clustered of single mass ,
- not capable of indefinite growth
- not able to invade healthy surrounding tissue
Malignant defintion
A tumour that continues to grow and becomes progressively more invasive
What is Metastasis
Metastasis is the ability of a malignant tumor to form 2 (degree) tumors (metastases) at other sites in
the body.
What is Metastatic potential
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
Where do sarcoma arise and give examples
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].
Examples of non - epithelial cancers and where they originate
- 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,
Tumor-suppressor genes
allow cancer cell survival when they fail
usually “loss of function mutations”
generally recessive eg Rb
Apoptosis
when faults-leads to abnormal cell survival
How does an oncogene cause cancer
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
Are tumors the result of a change in
DNA sequence
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)
Are tumors derived from a single
abnormal cell?
Various observations suggest that this is the case:
- 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.
- X Chromosome inactivation
What is the cumulative damage model
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
What are some examples of Inherited single gene defects and their Cancer Susceptibility
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
What is the difference between sporadic and familial retinoblastoma?
Familial (Hereditary): Multiple tumors, affecting both
eyes, early onset, 6x increased cancer risk
Sporadic (Non-hereditary): Single tumor,
affecting one eye, later onset
What “causes” cancer?
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
