Neoplasia IV-VI Flashcards
What is the most common type of mutation in inherited cancer syndromes?
Point mutation in a single allele of a tumor suppressor gene
What are three autosomal dominant inherited cancer syndromes and what is their associated mutation?
- Familial adenomatous polyposis - APC gene
- Li-Fraumeni syndrome - p53 gene
- MEN-1 and MEN-2 - transcription factors
What type of mutation contributes to development of the malignant phenotype?
Driver mutations
What type of mutation leads to genomic instability and greatly increases the frequency of mutations?
Passenger mutations
What type of mutation maintains genomic integrity and appears to be a common early step on the road to malignancy?
Loss-of-function mutations
What are two epigenetic modifications that can lead to cancers?
- DNA methylation
2. Modifications of histones
Name the 8 key changes in malignancy.
- Self sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Evasion of apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Ability to invade or metastasize
- Defects in DNA repair
- Altered cellular metabolism
What cytokine are many tumor cells resistant to?
TGF-beta
What is the name of genes that promote autonomous cell growth in cancer cells?
Oncogenes
What is the name of genes that promote normal cell growth and development?
Proto-oncogenes
What are the three ways oncogenes can be activated?
- Change in gene structure
- Gene amplification
- Change in gene regulation
What are the three variants of the RAS oncogene in humans?
HRAS, KRAS, NRAS
What is the single most common abnormality of proto-oncogenes in human tumors?
Point mutation in RAS family of genes
What gene is a serine/threonine protein kinase that is upstream of the MAPK family of serine/threonine protein kinases?
BRAF
What gene activates a cascade of serine/threonine kinases including AKT?
PI3K
What cancer involves a BCR-ABL tyrosine kinase as a result of a chromosomal translocation? What chromosomes does it involve?
Chronic myelogenous leukemia
9 –> 22
Name a class of nonreceptor tyrosine kinases that can be activated by point mutations?
JAK-STAT
Name the transcription factor that is most commonly involved in human tumors.
MYC
What enzyme can MYC upregulate that allows it to reprogram somatic cells into pluripotent stem cells?
Telomerase
Which cyclin is overexpressed in breast, esophagus, liver, and some lymphomas?
Cyclin D
Amplification of what CDK gene occurs in melanomas, sarcomas, glioblastomas?
CDK4
What are some examples of tumor suppressor genes?
- Rb (retinoblastoma)
- p53
- BRCA 1&2
- APC
What is the name of the syndrome that involves inheritance of a mutated copy of p53?
Li-Fraumeni syndrome
What are the three interlocking mechanisms p53 uses to thwart neoplastic transformation?
- Activation of temporary cycle arrest (quiescence)
- Induction of permanent cell cycle arrest (senescence)
- Triggering of programmed cell death (apoptosis)
