Lecture 5 Flashcards
Helicobacter pylori causes
Chronic inflammation via stomach ulcers, increasing risk of cancer.
What % of cancers are environmental vs hereditary?
90-95% enviro, 5-10% hereditary
Rous sarcoma
Naturally occurring retrovirus, first oncovirus described
DNA viruses that contribute to cancer
HPV (cervical, penile, anal), Epstein-Barr (herpes) (Burkitt’s lymphoma), Hep B (liver carcinoma).
RNA viruses that contribute to cancer
Human T-cell leukemia, Hep C (liver carcinoma), retroviruses and endogenous viruses.
3 main retrovirus genes
Pol, env, gag
Retroviruses cause tumors in two ways
- Acute transforming viruses 2. Non acute (chronic) transforming viruses
Acute transforming viruses
Carry oncogenes in their RNA genome, CAN transform cells in culture
Non-acute (chronic) transforming viruses
Don’t carry oncogenes, CANNOT transform cells, tumorigenesis occurs over time
Viral oncogene
Gene from the virus itself
Non-viral oncogene
Proto-oncogene or oncogene stolen from host cell, typical in its inactive form. Can incorporate with retroviral genome and yield a highly oncogenic retrovirus.
Oncolytic viruses
Attenuated virus that targets, infects, and kills cancer cells specifically.
Mutations in the sperm or egg
Germline mutations
Mutations in adult differentiated cells
Somatic mutations
The degree to which a possessed trait is expressed
Penetrance
The number of carriers of a specific allele in a population at a given time
Prevalence
How is the function of mutated proto-oncogenes impacted?
Mutations in proto-oncogenes are gain of function mutations
How many mutated alleles are necessary for oncogenic expression?
One mutated allele –> dominantly acting
Four mechanisms of oncogene activation
Retroviral integration, deletion/point mutation, gene amplification, chromosomal rearrangement (translocation).
Retroviruses can bring a strong ____ close to the proto-oncogene to activate it
Promoter
Mutations can alter ____
Protein activity
Gene amplification can lead to
Overexpression
Fusion proteins with cancerous activity can be generated by
Chromosomal rearrangements
Chromosomal rearrangements can activate proto-oncogenes by
Bringing a string enhancer close to the gene
The three most common coded-for domains of oncogenes are
Protein kinases, DNA binding, transcriptional regulation
Philadelphia chromosome
9;22 translocation, fuses bcrl and c-abl
Oncogene that helps transmit extra cellular growth signals to the nucleus
Ras
Mutated Ras is locked into its activated conformation by
A mutation that prevents it from hydrolyzing it’s attached GTP
Nuclear oncogene that acts as a transcription factor
MYC
What does MYC regulate?
Genes affecting apoptosis, proliferation, and immortalization
What events can activate MYC?
Retroviral insertion, chromosomal rearrangement, gene amplification
