case 4 - cancer Flashcards
what are the two classifications for cancer
familial cancers
sporadic cancers
what are the features of familial cancers
1% of all cancers
Single gene mutations (Mendelian disorders)
Most are inherited as autosomal dominant traits
Most due to inherited mutations of tumour suppressor genes
Further genetic events are necessary if the mutation is in somatic cells. Even though the mutated gene is inherited, it isn’t sufficient for malignancy
what are the features of sporadic cancers
99% of all cancers
Result of exposure to carcinogenic agents and unprepared DNA replication errors
Results in somatic activation/inactivation of cancer genes
what type of onset is familial cancer
early onset
what are the features of the cells in familial cancers
tumour cells - both copies of TSG inactivated
all other cells - one copy of TSG inactivated
what is the onset of sporadic cancers
late onset
what are the features of the cells in sproadic cancer
Tumour cells: both copies of tumour suppressor genes inactivated
All other cells: normal
what is an adenoma
cancer of the glands
what is a carcinoma
epithelial cells - 90% of all cancers
what is a lymphoma
lymphocytes or lymphatic tissue
what is a sarcoma
connective tissue
what is a blastoma
immature / pre-cursor cells - dendrites - WBCs
what is a papilloma
surface epthelial
what are the two types of cancer genomic instability
Either chromosomal instability - result of many numerical and structural abnormalities
Or microsatellite instability - result of impaired DNA mismatch repair (MMR)
what is telomerase
an enzyme that prevents the shortening of the telomere, thus preventing senescence
what happens in normal cells
telomerase is switched off
what happens in malignant cells
telomerase is switched on, thus inhibiting senescence
what is sensence
specific number of cell divisions
what does successful carcinogenesis require
either mutations that increase the rate of cell proliferation, so as to provide an expanded target for further mutations (clonal evolution)
or
mutations that destabilise the genome, so as to increase the rate of further mutations
to be successful, what must a malignant cancer cell have
Become independent of external growth signals
Become insensitive to external anti growth signals
Become able to avoid apoptosis
Become capable of indefinite replication
Become capable of sustained angiogenesis
Become capable of tissue invasion and metastasis
what is cancer mediated by
oncogenes and TSGs
telomeres
Wnt and Ras
CIN/MMR
p53 and apoptosis
cyclin,CDK, CDi
features of (proto) oncogenes
gain of function
dominant - only need one mutated allele to be activated
features of tumour suppressor genes
loss of function
recessive - need two mutated alleles to be inactivated
what is a proto oncogene
is a normal gene that may be activated into an oncogene due to mutations or increased expression
what do proto oncogenes promote
cell division, survival and growth
what are the four ways in which proto oncogenes can be activated into oncogenes
Point mutations that increase protein function
Gene amplification that causes over expression
Chromosomal translocation e.g MYC
Viral stimulation that may lead to addition/deletion of genes when viral DNA is integrated with human DNA
what is MYC
it is a regulator gene that codes for a transcription factor. if translocated, MYC will continually be expressed, causing unregulated expression of many genes, some of which are involved in cell prolideration e.g cyclin D1 and result in the formation of cancer
what is an oncogene
a gene that has the potential to cause cancer
what are two examples of oncogenes
b catenin and KRAS
what happens when one allele of oncogenes is mutated
there is a gain in protein function
what do oncogenes usually code for
- Secreted growth factors (EGF, Wnt, Ras)
- Cell surface receptors (HER)
- Signal transduction system components (ABL)
- Nuclear proteins transcription factors (MYC)
- Cyclins/cyclin dependent kinases (Cyclin D1, CDK4)
what are tumour supressor genes
body’s natural defence mechanism against malignancy
what happens when both alleles of TSGs are mutated
there is a loss of protein function
what is inactivation of TSGs caused by
Mutations
Chromosomal abnormalities
Methylation of promoters
Interaction with viral proteins
what is worse, loss of TSG or activation of oncogenes
loss of TSG
what is the function of tumour suppressor genes
inhibit progress through the cell cycle -CKi’s - p21
promote apoptosis
inhibit cell growth
DNA repair
cell adhesion to prevent metastasis
all cancers metastisise except
glial cells of the CNS, these usually form benign tumours
basal cell carcinomas of the skin
what are the three pathways via which cancer spreads
direct seeing of body cavities or surfaces
Lymphatic spread
Hematogenous spread - blood
