Personalised and Stratified Medicine

Question 1

Name three different types of DNA sequencing

Answer 1

Whole genome sequencing, whole exome sequencing and target sequencing (looking at specific genes)

Question 2

What were the three main classes of breast cancer before poly-omic studies?

Answer 2

> Oestrogen receptor positive
HER2 receptor positive
Triple negative - progesterone receptor negative, ER- and HER2-

Question 3

What are the four main types of cancer derived from poly-omic analysis?

Answer 3

Luminal A, luminal B, basal-like and HER2+

Question 4

What are the four subtypes of cutaneous melanoma?

Answer 4

BRAF mutant, RAS mutant, NF1 mutant and triple wild type

Question 5

Outline what is meant by BRAF mutant melanoma

Answer 5

BRAF V600E is the most common mutation which leads to gain of function of the gene. This mutation leads to over-activation of the RAF/MEK/ERK signalling pathway to increase cellular proliferation, and therefore BRAF and MEK inhibitors are effective

Question 6

How may BRAF mutant melanoma be treated?

Answer 6

> BRAF V600E inhibitor is vemurafenib and dabrafenib

> MEK inhibitor is trametinib

Question 7

Outline what is meant by RAS mutant melanoma?

Answer 7

NRAS-Q61 is the most common and leads to a gain of gene function

Question 8

How may RAS mutant melanoma treated?

Answer 8

NRAS mutations also lead to over-activation of the RAF/MEK/ERK signalling pathway, and can be treated with MEK inhibitors such as trametinib

Question 9

Outline what is meant by triple wild type melanoma

Answer 9

KIT, GNAQ and GNA11 mutations which mostly lead to a gain of function

Question 10

Describe the pathogenesis of follicular lymphoma

Answer 10

There is a fusion oncogene known as IGH-BCL2 which leads to the over-expression of the anti-apoptotic protein BCL-2

Question 11

How is follicular lymphoma diagnosed?

Answer 11

There is a translocation between chromosome 14 and 18 in the germinal centre B cells in the lymph nodes