W07_03 Molecular pathogenesis of cancer - common genes Flashcards
what kinds of mutations are there in cancer?
point;
insertion/deletion;
amplification/copy number alteration;
translocation/chromosomal rearrangement
define oncogene
promotes autonomous growth in cancer cells, in the absence of cell growth-promoting signals
define proto-oncogene
non-mutated, “normal” gene with the potential to become oncogenic.
define oncoprotein
the product of an oncogene
typically, oncoproteins can be of these signalling types
growth factors; growth factor receptors; signal transduction molecules; nuclear regulatory proteins; cell cycle regulators
what class of signalling is Her2-neu?
growth factor receptor
what happens to Her2-neu in cancer?
gene is amplified, and the receptor is increased as a result
what’s the clinical significance of a Her2-neu mutation?
gives rise to breast cancer;
25-30% of breast cancers express this on the surface
treatment for Her2-neu+ breast cancer?
trastuzumab (Herceptin) targeted therapy
what class of signalling is Ret?
growth factor receptor (normally a glial-derived neurotrophic factor receptor)
when is ret normally expressed?
during neural development, and also in neuroendocrine cells
where is ret normally expressed?
C-cells of thyroid, adrenal medulla, parathyroid cells
which clinical diseases are caused by ret mutation (usually germ-line mutation)?
multiple endocrine neoplasia type ii,
familial medullary thyroid cancer
what class of signalling is Ras?
receptor-associated signal transduction molecule
what are the three most well known Ras oncogene types?
HRas,
KRas,
NRas
how can Ras become problematic?
if the pathway of GTPase is blocked, then Ras will stay constitutively active
ras helps us guide treatment for which type of cancer?
lung
what class of signalling is Abl?
non-receptor associated tyrosine kinase
what mutation leads to a problem with abl?
when abl translocates onto chromosome 22 and makes bcr-abl
what disease results from bcr-abl?
cml and all
chronic myeloid leukemia and acute lymphoblastic leukemia
therapy for bcr-abl?
imatinib mesylate
what class of signalling is Myc?
nuclear regulatory protein
how can myc go wrong?
thru amplification or translocation
n-myc is amplified to in which cancer?
neuroblastoma
l-myc is amplified in which cancer?
SCLC
what’s a “double minute”?
copies of a gene that float around, independent of a chromosome
what’s the molecular cause of burkitt’s lymphoma?
translocation of the myc gene to the IgH gene
what class of signalling is cyclin D?
cell cycle regulator
cyclin D associates with which two factors to help cell cycle regulation?
CDK4 and CDK6
