Cancer (easy)

Question 1

Suggest effect of mutation of BRAF gene [2]

Answer 1

1. GIF mutation: POG to OG
2. BRAF protein has altered 3D conformation
3. BRAF protein is hyperactive / degradation-resistant
   » active even in absence of GF / activated RAS

Question 2

Suggest how (mutated BRAF&raquo_space; phosphorylation cascade&raquo_space;) phosphorylated ERK contributes to cancer [2]

Answer 2

1. Phosphorylates cyclin-CDK complexes

2. Causes cells to bypass G1/S checkpoint&raquo_space; uncontrolled CD

Question 3

Explain why a mutation in the BRAF gene alone may not cause cancer [4]

Answer 3

1. Cancer is a multi-step process
   » requires accumulation of independent mutations

… for excessive CD

2. Need to accumulate LOF mutations of many TSGs&raquo_space; unable to (function)
3. At least one GOF mutation of POG&raquo_space; overexpression of GFs / hyperactive GFs
4. Loss of contact inhibition
5. Activation of genes coding for telomerase&raquo_space; divide indefinitely
6. Angiogenesis&raquo_space; transport oxygen and nutrients
7. Metastasis&raquo_space; invade and enter blood&raquo_space; travel to form secondary tumours

Question 4

Describe how translocation of the bcl2 gene influences its Tsc [3]

Answer 4

1. bcl2 gene regulated by a normal promoter
   » now under influence of an ENHANCER of another gene
2. STFs - ACTIVATORS bind to enhancer
   » promote BENDING OF SPACER DNA
   » interact with GTFs and RNA pol
3. Promote assembly of TSC IC at the promoter
   » increase Tsc frequency

Question 5

Compare POGs with TSGs

Answer 5

1. GOF vs LOF
   - produced excessively / hyperactive
   - not produced / non-functional
2. Dominant vs recessive
   - mutation in 1 allele sufficient
   - mutation in both alleles needed
3. Function

Question 6

State an ethical consideration when screening for inherited forms of cancer [1]

Answer 6

1. Respect for individuals’ personal choices

2. May result in unintended discrimination by insurance/employment agencies

Question 7

Explain the importance of CC checkpoints [2]

Answer 7

1. G1, G2 and M checkpoints only allow the cell to proceed to the next stage
   » if the previous phase has been completed without mistakes in DNA replication
   » and DNA is not damaged
2. Importance: prevent uncontrolled CD

Question 8

Explain how defective checkpoint control in interphase can lead to cancer [3]

Answer 8

1. Defective checkpoint control in G1 and/or G2
   » allows cells with inaccurate DNA replication / damaged DNA to pass on the mutation to the daughter cells
2. As cells continue to divide, mutations accumulate in a single cell
   » GIF mutation in POG + LOF mutation in TSG