Part 3

A tumour suppresor that has active DNA repair processes

Arrests cell division if damage is severe 

Over half of human cancers have this mutation 

Also detects metabolic stress, hypoxia, dysregulated growth

Congenital TP53 mutation 

AKA Hereditary non-polyposis colorectal cancer 

Makes patients prone to many cancers: 

Colorectal

Endometrial 

Small bowel 

Ureter 

Renal 

Pelvis 

Weakness and wasting of the body 

Promote cell growth and proliferation 

Regulation of apoptosis 

Regulation of differentiation 

Regulation of cellular life span

These are examples of? 

Ras(G12V)

Bcl-2 (over expression of anti-apoptitic Bcl-2) 

BCR-ABL (reciprocal translocation between C9 and C22 - CML) 

Elevated expression of EGFR is commonly seen in what cancers? (2)

Requires loss of both alleles to result in dysregulation

Targets the M phase of the cell cycle to prevent it 

Therefore preventing rapid growth of cells 

A major cell cycle regulator 

Blocking transcription of E2F responsive genes, preventing the cell entering S phase 

Loss of this will therefore lead to loss of growth suppression 

Tumour composed of normal cells / tissues, present in an abnormal place 

Tumour composed of disorganised growth of different cell types normally present in that organ

Tumour composed of derivatives of all three embryological layers 

Virus that can cause:

Hodgkins lymphoma 

Nasopharyngeal carcinoma 

Kaposi's sarcoma 

4 classes of normal genes that are damaged in carcinogenesis 

Her2-neu (oncogene)

Kras (oncogene)

BRAF (oncogene)

Examples of what types of genes: 

BRCA 1 and 2 (double strand repair)

MMR genes (single nucleotide changes, very important pathway in Lynch syndrome) 

What gene mutation are these treatment methods targeting: 

Platinum based chemotherapies (carboplatin) - induces DNA cross links, cannot be repaired by gene deficient tumours due to defective homologous recombination - results in cell death 

PARP inhibition:

Accumulation of single strand DNA breaks - subsequently converted to ds DNA breaks - lethal to gene deficient cells 

MMR genes: 

MLH1 

MSH2 AND 6

PMS 2 

Dominantley inherited 

Blocks the immune systems response to High-microsatellite instability (MSI-H) 

Instability in short tandem repear sequences (microsatellite) is in mutated mismatch repair genes 

Pembrolizumab 

30% of patients with NSCLC will develop? 

Symptoms: 

Thirst, constipation, depressed and then confused 

Due to PTHrP release, stimulated resorption of bone 

15% of patients with SCLC develop? 

Incresaed H20 absorption at distal tubule and hence hyponatraemia 

F < 130 and M < 125 = confused state and seizures 

Breast cancer = 70% 

Second primary breast cancer = 65% 

Ovarian cancer = 45% 

Prostate cancer (M) = 15% 

Breast cancer = 70% 

Contralateral breast = 65% 

Ovarian cancer = 20% 

Male: 

Breast = 8% 

Prostate = 25% 

Pancreatic = 3% 

Breast cancer gene panel 

Caused by a mutation in the APC gene 

Rare <1%, cause of CRC 

95% will have polyps by the age of 35 

Breast = 11% 

Colorectal = 4% 

Prostate = 2% 

Ovarian = 1% 

Stomach = 1% 

Pancreatic = 1% 

Male breast cancer = 1% 

Current cancers screened in the UK 

Ability of the test to correctly identifty those who have the disease 

True positive 

Ability of test to correctly identify those who do not have the disease 

True negative 

Females aged 25-64 

25-49 every 3 years 

50-64 every 5 years 

Both preventative and early detection

Virus associate with 70% of cervical cancer cases 

FOBT every 2 years from 60-74 

Flexible sigmoidscopy from 55y/o 

High risk - risk intervention = full colonscopy 

Both preventative and early detection 

50-70 every 3 years 

2 view mammogram 

Not preventative but reduction in mortality 

30-40 annual MRI 

40-50 annual MRI and mammogram 

50+ annual mammogram