Day 8, Lecture 1 (Aug 31): Cancer III: Environment, Models, and Targeted Therapeutics Flashcards
Aflatoxin
- From grain and peanuts contaminated with Aspergillus
- Cancer:
- Hepatocellular carcinoma
- Mechanism:
- Reactive metabolite causing DNA damage
asbestos (silicate minerals) cause what kind of cancer
- Mesothelioma
- mechanism: unknown
Cigarette smoke (contains 3,4-benzpyrene) causes what cancer and how
- lung cancer
- mechanism:
- Reactive metabolite causing DNA damage
radiation (ionizing) causes what kind of cancer and how
- cancer:
- leukemia, thyroid cancer
- Mechanism:
- mutations, genome-level breakage
Sunlight (UV light) causes what cancer and by what mechanism
- Cancer:
- Carcinoma
- Melanoma
- Mechanism:
- Pyrimidine dimers
Aflatoxin leads to DNA adducts and mutation of ____
- p53
Human papillomavirus (HPV) causes _____ cancer
- 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)
What is dysplasia
abnormal, disorderly growth
HPV proteins bind to what
- HPV protein E6 binds to p53
- HPV protein E7 binds to RB
Human Herpes virus 8 (HHV-8) causes what kind of cancer
- body cavity lymphoma
- Kaposi Sarcoma
Epstein-Barr virus (EBV) causes what kind of cancer
Burkitt lymphoma
Human papilloma virus (HPV) causes what kind of cancer
Cervical carcinoma
Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause what kind of cancer
Hepatocellular carcinoma
Colorectal carcinomas can arise in a stepwise fashion, explain
What is the difference between FAP (familial adenomatous) and Hereditary non-polyposis colon cancer (HNPCC/Lynch syndrome)
- 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
What is the common treatment for FAP
prophylactic colectomy because colorectal cancer risk is 100% at 50 years old
are microsatellites scattered throughout the genome
yes
FAP is caused by a mutation in
APC (5q21)
Explain how the microsatellite instability pathway can result in colonic adenocarcinoma
- 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
What is KRAS
- 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
About half of melanomas have ____ mutations
BRAF
What is BRAF
- signal transduction protein downstream of KRAS
- About half of melanomas have BRAF mutation
Melanomas with _______ mutation respond to BRAF kinase inhibitors such as _____
- BRAFV600E (valine to glutamate at amino acid position 600, i.e. a missence mutation normally mutation is T to A)
- Vemurafenib
can mRNA be extracted from cancer and quantified
- Yes
- it can show the gene expression and the need for more or less aggressive therapy
There are how many molecular building blocks of life
68
What is systems biolgy
quantify systems components and group into networks
