Molecular testing it the diagnosis of cancer

Question 1

Name the major genes being targeted by novel therapies

Answer 1

1. BCR/ABL: chronic myelogenous leukemia
2. HER2: Breast cancer. Indication for herceptin.
3. EGFR: NSCLC target: tyrosine kinase
4. KRAS: colorectal cancer
5. BRAF: melanoma

Question 2

High density microarrays can:

Answer 2

1. Analyze whole genome copy #
2. LOH
3. somatic mutations
4. tumor suppressor + oncogenes

Question 3

Describe common molecular pathology techniques used to characterize cancer

Answer 3

1. RT PCR
2. DNA sequencing
3. Array

Question 4

PGXm

Answer 4

measure of how well a patient metabolizes a drug. If it’s too slow, there is no response. If it is too fast, the drug is not around long enough to have an effect

Question 5

PGXt

Answer 5

Predicted toxicity risk based on pt’s genetics

Question 6

What does diagnostic mutation analysis test for?

Answer 6

biomarkers indicating a large population of undifferentiated or immature cells

Question 7

Which types of HPV cause cancer?

Answer 7

HPV 16 & 18 account for majority of cancers

Question 8

What does quantitative molecular oncology testing do?

Answer 8

Tests for minimal residual disease or tumor burden. Examines the amount of abnormal BCR/ABL gene (philadelphia chromosome) load using RT-PCR.

Question 9

What is minimal residual disease?

Answer 9

The remaining number of leukemia cells during treatment. It’s a major cause of relapse.

Question 10

What is hematologic response?

Answer 10

normal Pb (peripheral blood) values and spleen size

Question 11

What is cytogenic response?

Answer 11

Blood smear analysis.
0% Ph+ cells: complete cytogenic response
1-35% Ph+ cells: partial cytogenic response

Question 12

What is a molecular response?

Answer 12

Reduction or elimination of bcr-abl in mRNA in marrow or peripheral blood

Question 13

What is the process of treatment with personalized medicine?

Answer 13

1. Examine predisposition through chromosome analysis
2. screening
3. diagnosis/prognosis
4. right drug
5. monitoring

Question 14

How does irinotecan work? How does it illustrate the use of personalized medicine?

Answer 14

Treatment for colon cancer. Some have a very bad response to the drug because their UGT1A1 has an additional gene repeat sequence, preventing inactivation leading to severe diarrhea and bone marrow toxicity. Can now analyze which pts have that additional repeat sequence.

Question 15

What is targeted therapy?

Answer 15

Drugs that attack the molecular basis for cancer, in order to target tumor cells while leaving normal cells intact. Historically, chemotherapy has been nondiscriminative. The first targeted therapy is herceptin.

Question 16

What is qualitative molecular testing used for?

Answer 16

Tests for translocation of chromosomes

Question 17

how do anti-EGFR therapies work?

Answer 17

They turn off the EGFR signals either through monoclonal antibodies or small cell tyrosine kinase inhibitors (erlotinib or gefitinib)

Question 18

What mutation in EGFR is associated with resistance?

Answer 18

T790M

Question 19

What type of molecular information is being provided by the various test below?

1. quantitative diagnostic mutation analysis
2. quantitative molecular oncology testing
3. genotyping

Answer 19

1. quantitative diagnostic mutation analysis: identifies loss of differentiation
2. quantitative molecular oncology testing: gene copy #, tumor burden, gene expression
3. Determines primary vs. treatment response