Molecular Basis of Neoplasia Flashcards
What are the three typical ways in which a proto-oncogene may become an oncogene?
Mutation (insertion, deletion, point), gene rearrangement (translocation), gene amplification
What are the most important cell cycle regulators mutated in cancers that disrupt the cell cycle?
Cyclin D-CDK4/6
True/False. Increased production of growth factors is enough for neoplastic transformation.
False. Other mutations or function gains must take place, such as promotion of cell division or inhibition of cell death.
True/False. Oncogenes are genetically dominant.
True. The presence of one abnormal allele will override expression of the normal allele.
What genes promote apoptosis?
Bax, bad, bid
What oncogene is expressed in a large number of human tumors and promotes autocrine growth?
c-sis-proto-oncogene (PDGF-B)
What genes are responsible for DNA mismatch repair and are mutated in some cancers?
MSH2, MLH1
What growth factor receptor is expressed in a large majority of breast cancers?
HER2
The loss of this gene in some cancers causes overstimulation of the PI3K/AKT pathway.
PTEN
Nearly all growth factor receptors, when bound by a ligand or mutated, act via what mechanism?
Tyrosine kinase
What two genes are highly associated with breast and ovarian cancers?
BRCA-1 & BRCA-2
What is the phenomenon haploinsufficiency?
Some cancers may occur without mutations of tumor suppressor genes. In these cases, protein expression of these genes may be reduced, thus disrupting the homeostatic balance
What gene is overexpressed in follicular B cell lymphoma to prevent apoptosis?
BCL2
What is Lynch Syndrome?
Colon cancer due to failed DNA mismatch repair
What gene mutation is associated with Familial Adenomatous Polyposis and non-familial colorectal carcinomas?
APC - functions in the Wnt pathway. Mutation inhibits B-catenin degradation
What mutation is the single most common abnormality of dominant oncogenes?
Ras gene mutations - Ras remains phosphorylated and transcription factors are continuously activated
True/False. TGF-B acts only as a tumor suppressor that inhibits the cell cycle and promotes apoptosis.
False. While this is true during early cancer development, TGF-B is known to promote tumor proliferation as development continues.
What is Xeroderma pigmentosum?
Skin cancer caused by a failure to repair thymine dimers due to skin exposure. Associated with MSH2 & MLH1 mutation
What is the most common mutated tumor suppressor gene?
p53
Chronic Ras activation is associated with what gene mutation?
NF-1
What enzyme has led to the immortalization of some tumor cells?
Telomerase
What are oncogenes?
Mutated forms of proto-oncogenes that gain function and promote the cell proliferation and/or inhibit cell death.
Mutation of Cyclin D-CDK4/6 casues…?
G1 progression to S phase of the cell cycle. Once the cell enters the S phase, entry into the cell cycle is irreversible
What are the normal functions of BRCA-1 & 2?
Double strand DNA break repair
True/False. Both alleles of tumor suppressor genes must be mutated in order for a loss of function.
True. A single mutation may increase risk of cancers, but the gene still maintains tumor suppressor function.
What disorder is caused by a rare autosomal dominant mutation of p53?
Li Fraumeni Syndrome
What two cancers are associated with MSH2 & MLH1 mutations?
Xeroderma pigmentosum & Lynch Syndrome
A mutation of what gene causes dysregulation of Cyclin D-CDK4/6?
p16 / INK4a gene
What is the normal function of Rb?
When hypophosphorylated, Rb binds E2F to inhibit the cell cycle. Hyperphosphorylation of Rb causes it to break away from E2F and promote entry into the cell cycle. This occurs in some cancers
What gene is activated by p53 to inhibit Cyclin E and halt the cell cycle?
p21
True/False. Epigenetic factors can result in cancer.
True. Hypermethylation, especially of tumor suppressor genes, can cause cancer.
What disorder is associated with PTEN mutation?
Cowden Syndrome
What is one of the most common transcription factors abnormally expressed in cancer?
Myc
