Day 8, Lecture 1 (Aug 31): Cancer III: Environment, Models, and Targeted Therapeutics

Question 1

Question 2

Question 3

Aflatoxin

Answer 3

• From grain and peanuts contaminated with Aspergillus
• Cancer:
  
  • Hepatocellular carcinoma
• Mechanism:
  
  • Reactive metabolite causing DNA damage

Question 4

asbestos (silicate minerals) cause what kind of cancer

Answer 4

• Mesothelioma
• mechanism: unknown

Question 5

Cigarette smoke (contains 3,4-benzpyrene) causes what cancer and how

Answer 5

• lung cancer
• mechanism:
  
  • Reactive metabolite causing DNA damage

Question 6

radiation (ionizing) causes what kind of cancer and how

Answer 6

• cancer:
  
  • leukemia, thyroid cancer
• Mechanism:
  
  • mutations, genome-level breakage

Question 7

Sunlight (UV light) causes what cancer and by what mechanism

Answer 7

• Cancer:
  
  • Carcinoma
  • Melanoma
• Mechanism:
  
  • Pyrimidine dimers

Question 8

Aflatoxin leads to DNA adducts and mutation of ____

Answer 8

• p53

Question 9

Human papillomavirus (HPV) causes _____ cancer

Answer 9

• HPV causes cervical cancer
• Can cause some oropharyngeal squamous cell carcinomas
• Human Papillomavirus
  
  • sexually transmitted
  • dsDNA virus
  • 40 types (of about 100) infect female GU tract
    
    • high-risk types such HPV 16 and 18: vervical dysplasia and cancer
    • low-risk types: condyloma (genital warts)
  • only a minority of infected women develop cervical cancer
• Prevention: Gardasil (doesn’t cover all types)

Question 10

What is dysplasia

Answer 10

abnormal, disorderly growth

Question 11

HPV proteins bind to what

Answer 11

• HPV protein E6 binds to p53
• HPV protein E7 binds to RB

Question 12

Human Herpes virus 8 (HHV-8) causes what kind of cancer

Answer 12

• body cavity lymphoma
• Kaposi Sarcoma

Question 13

Epstein-Barr virus (EBV) causes what kind of cancer

Answer 13

Burkitt lymphoma

Question 14

Human papilloma virus (HPV) causes what kind of cancer

Answer 14

Cervical carcinoma

Question 15

Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause what kind of cancer

Answer 15

Hepatocellular carcinoma

Question 16

Colorectal carcinomas can arise in a stepwise fashion, explain

Answer 16

Question 17

What is the difference between FAP (familial adenomatous) and Hereditary non-polyposis colon cancer (HNPCC/Lynch syndrome)

Answer 17

• in FAP the colon is carpeted with polyps while in HNPCC the colon has a few polyps
• both are autosomal dominant
• HNPCC is caused by mutations in mismatch repair genes MLHI, MSH2, MH6, and PMS2
• FAP is caused by mutation in APC (adenomatous polyposis coli; 5q21): tumor suppressor
  
  • missense mutations and deletions
• FAP has 100% colorectal cancer risk at 50 years while lynch syndrome has 80% colorectal cancer risk at age 44

Question 18

What is the common treatment for FAP

Answer 18

prophylactic colectomy because colorectal cancer risk is 100% at 50 years old

Question 19

are microsatellites scattered throughout the genome

Answer 19

yes

Question 20

FAP is caused by a mutation in

Answer 20

APC (5q21)

Question 21

Question 22

Explain how the microsatellite instability pathway can result in colonic adenocarcinoma

Answer 22

• Microsatellites have STR (short tandem repeats) these can get mismatched if the polymerase slips thus leading to a loop, which if not fixed leads to a longer allele

Question 23

What is KRAS

Answer 23

• KRAS is a GTPase, signaling protein
• mutated in colorectal carcinoma, pancreatic adenocarcinomas, and others
• Colon cancer: about 50% have point mutations in KRAS
• KRAS mutations predict decreased responsiveness to monoclonal Ab therapy against epidermal growth factor receptor (EGFR) (e.g. cetuximab, panitumumab)
• mutations nomrally occur when A is substituted for T in codon 61

Question 24

About half of melanomas have ____ mutations

Answer 24

BRAF

Question 25

What is BRAF

Answer 25

* signal transduction protein downstream of KRAS * About half of melanomas have BRAF mutation

Question 26

Melanomas with _______ mutation respond to BRAF kinase inhibitors such as \_\_\_\_\_

Answer 26

* BRAFV600E (valine to glutamate at amino acid position 600, i.e. a missence mutation normally mutation is T to A) * Vemurafenib

Question 27

can mRNA be extracted from cancer and quantified

Answer 27

* Yes * it can show the gene expression and the need for more or less aggressive therapy

Question 28

Answer 28

Question 29

Question 30

There are how many molecular building blocks of life

Answer 30

68

Question 31

What is systems biolgy

Answer 31

quantify systems components and group into networks

Question 32

Question 33

Question 34

Question 35