cancer diagnosis

Question 1

Name the major genes being targeted by novel therapies mentioned in lecture.

Answer 1

BCR-ABL

HER-2

EGFR activating mutations (exon 19 and 21)

KRAS

Question 2

Describe common molecular pathology techniques used in characterizing cancer.

Answer 2

Real Time PCR
  o Allele specific PCR
• DNA Sequencing
  o Sanger
  o Next generation

• Array
o Microfluidic cards (low density)
o Beads array (medium density)
o Microchips (high density)

Qualitative Testing

• B and T-cell Lymphomas

• Capillary PCR to determine if there is a clonal population
• Next Generation Sequencing

• HPV

• 6 and 11: Low risk, genital wart
• 16 & 18: High risk, pre-cancer changes
• Cobas 4800 System
  o automated PCR)
  o Identify the type of HPV
  Quantitative Testing

• Philadelphia chromosome CML disease

• BCR-ABL sequence

Question 3

Identify common gene mutations in neoplasia associated with resistance to therapy.

Answer 3

There was no answer

Question 4

Define what personalized medicine entails.

Answer 4

• Same diagnosis for a group of patients but subsets will respond differently to different

drugs, no that before you begin testing

• Irinotecan

• Typoisomerase inhibitr that slows down tumor growth
• UGT1A1 reduced expression in some individuals but needed to metabolize the drug
• So people who have low UGT1A1 get a buildup of toxic Ironotecan

Question 5

Discuss how targeted therapy works.

Answer 5

• Tamoxifen
- Estrogen receptive tumors

• Herceptin
- MAB for breast cancers where HER-2 gene is amplified

• Anti-EGFR and Anti-ALK Therapies

- Adenocarcinoma

Question 6

Explain how quantitative molecular testing can assess the existence and amount of residual disease in some neoplasms.

Answer 6

• Gene copy number
• Minimal Residual Disease/Tumor burden
• Gene expression profiling
• Detection, prognosis, progression & therapeutic response & recurrence

Question 7

Discuss the role of EGFR and anti-EGFR treatment in certain neoplasm.

Answer 7

• EGFR = Growth factor receptor
• MAB & Tyrosine kinase receptors used to try and block the receptors
• Risk of developing “resistant” mutations
• KRASo Constutively expressedo Anti-EGFR drugs will be unresponsive since KRAs further in the pathwayo Colorectal cancer and lung cancers

Question 8

Important Points, Concepts and Specific Examples:

Answer 8

1. Diagnosis, prognosis, therapeutic management
2. Genotyping
3. Personalized medicine (irinotecan, herceptin, cetuximab)
4. Qualitative testing (gene rearrangements)
5. Quantitative testing (BCR-ABL1, HER2)
6. Genotyping (EGFR, KRAS)

Question 9

Important terms

Answer 9

Acquired mutations

BCR-ABL1

Cell cycle

Clonality

HER2

Human papillomavirus

Inherited mutations

Molecular pathology

Oncogenes

Replication

Tumor suppressor genes