Lecture 6 - Biomarkers

Question 1

What is a tumour profile?

Answer 1

Unique combination of DNA changes of a tumour

Question 2

Examples of proto-oncogenes

Answer 2

growth factors
• growth factor receptors
• signal transduction proteins (RAS)
• nuclear regulatory proteins
• cell cycle regulators

Question 3

Which cancer is caused by EGFR (ERB2) overexpression?

Answer 3

Squamous cell lung carcinomas

Gliomas

Question 4

KIT point mutation

Answer 4

Gastrointestinal stromal tumors

and other soft tissue tumors

Question 5

Kras point mutation 3

Answer 5

Colon carcinoma
Lung carcinoma
pancreatic carcinoma

Question 6

ABL translocation

Answer 6

CML and ALL

Question 7

Braf point mutation

Answer 7

Melanomas, Hairy cell

laeukemia

Question 8

Nuclear reg proteins examples

Answer 8

c-myc, n-myc, lmyc

Question 9

What are driver mutations?

Answer 9

mutations involved in

development or progression of a tumour:

Question 10

“actionable” drivers:

Answer 10

have significant
diagnostic, prognostic, or therapeutic implications in subsets of
cancer patients and for specific therapies

Question 11

What are passenger mutations indicative of?

Answer 11

indicative of a high mutation rate

resulting from carcinogens and DNA instability.

Question 12

What does the identification of biomarkers during anti cancer drug development lead to?

Answer 12

Increases chances of success

Accelerated drug approval process by providing effective patient stratification strategies in clinical trials

Question 13

Two types of biomarkers

Answer 13

Prognostic and predictive

Question 14

What do prognostic biomarkers give information about?

Answer 14

Disease outcome independent of treatment - or positive or negative for a mutation can be indicative of positive or poor prognosis

Question 15

What do predictive biomarkers give information about?

Answer 15

Disease outcome related to a treatment. I.e. Positive or negative for a mutation predicts response to a treatment.

Question 16

Two major types of NSCLC

Answer 16

Adenocarcinoma sand squamous cell carcinoma

Question 17

Adenocarcinoma characteristics

Answer 17

Arise in more distal airways
Have glandular histology
Express TTF1 and CK7

Question 18

Squamous carcinoma characteristics

Answer 18

Arise in more proximal airways
Squamous differentiation
Express ck 5/6, sox2, and p63

Question 19

2 biomarkers used in lung cancer

Answer 19

EGFR

ALK

Question 20

Two EGFR Inhibitors:

Answer 20

Gefitinib and erlotinib

Question 21

ALK mutation

Answer 21

Gene rearrangement in the EML4 gene and ALK GENE leads to constitutive activation of ALK in NSCLC

Question 22

How many percent of patients have EML4/ALK mutations?

Answer 22

4-5%

Question 23

Who are EGFR mutations seen in?

Answer 23

Women and non smokers

Question 24

Who are EML4/ALK mutations seen in?

Answer 24

Young people, non or light smokers with adenocarcinoma

Question 25

What’s is an ALK inhibitor?

Answer 25

Crizotinib

Question 26

Main biomarker in melanoma

Answer 26

BRAF V600E in half of melanomas

Question 27

What is an inhibitor of BRAF?

Answer 27

Vemurafenib is a selective inhibitor of BRAF in disseminated melanoma

Question 28

Role of pathologist in cancer therapy

Answer 28

Provide correct histological diagnosis of subtype

Request appropriate ancillary study to identify relevant biomarker

Question 29

How do you detect EGFR Mutation?

Answer 29

By immunohistochem, PCR or sequencing

Question 30

How is ELM4/ALK rearrangements detected?

Answer 30

FISH

Question 31

How are HER2 mutation detected?

Answer 31

Using immunohistochemistry or FISH

Question 32

How are BRAF mutations detected?

Answer 32

RT PCR, immunohistochemistry or next gen sequencing

Question 33

Two biomarkers used to diagnose T cell lymphoma

Answer 33

Icos and pd1