Scott: Breast Cancer Genetics Flashcards
where does breast cancer arise from within normal tissue?
epithelial layer
T or F: adult tissue contains stem and progenitor cells which provided capacity for growth throughout the lifespan?
true
_____ mutation affects all cells in the body
germline mutations (err or sperm)
____ mutation occurs in a cell in the body, only affects a single cell and its clonal descendants
somatic mutation
is a somatic mutation passed down through life of the individual and onto its offspring?
NO. not to offspring, NOT a germline mutations
inheritance of susceptibility (BRCA 1 and 2) is what type of inheritance pattern?
Autosomal dominant. inheritance of a single copy confers susceptibility
what does BRCA1 and 2 actually DO?
essential components of homologous recombination arm of DNA repair machinery, which then allows for genomic instability creating conditions for oncogenic somatic mutations to arise
in the _____ (absence or presence) of BRCA1, luminal progenitor cells accumulate
absence
what percentage of breast cancers are sporadic?
90%
subtypes differ in clinical characteristics: Luminal A has _____ (low, normal, high) levels of estrogen receptor, and therefore a _____ (worst, unchanging, best) prognosis?
HIGH. BEST.
subtypes differ in clinical characteristics: _____ is the overexpression of HER2 and the prognosis is improved with ______
HER2-amplified. Trastuzamab
subtypes differ in clinical characteristics: what type is often triple negative (NO ER, PR, no amp of HER2), BRCA mutations
BASAL-like
what treatments are used to block ER signaling in treating ER+ breast cancer?
Selective estrogen receptor modulators, aromatase inhibitors
ERalpha promotes transcription of secreted growth factor, such as _____
amphiregulin
extracellular estrogen controls proliferation of luminal cells _____ (direct/indirect)
INDIRECtly
tumor cells estrogen regulates growth _____ (direct/indirectly)
directly
How are tumor cells different than normal cells?
increase in # of cells expressing ER. change in which genes are regulated by ER binding
how are tumor cells NOT different than normal cells?
no mutations or amplifications of genes encoding estrogen or RE
how does ER promote transcription of a different set of genes in breast cancer?
overexpression of the pioneer transcription factor FOXA1
how does FOXA1 work?
it allows BINDING OF CLOSED chromatin at select sites and opens it and allows access to ER binding!!!!
what is one of the sites opened by FOXA1?
CYCLIN D1 promoter (therefore dysregulates proliferation)
what was the first SERM used to block E2/Er signaling in breast cancer?
Tamoxifen
________ type of drugs block synthesis of estrogen in non-ovarian tissues
Aromatase inhibitors. they DO NOT AFFECT THE ESTROGEN RECEPTOR
T or F: ERBB2 does require ligand binding for activation
FALSE. DOES NOT. increased ERBB2 expression, due to amplification allows dimerization to occur by mass action.
____ is a monoclonal antibody that binds extracellular domain of ERBB2 and blocks activity of its homodimers
Trastuzumab
____ is a small molecule inhibitor which binds and blocks kinase active site and blocks the EGFR-ERBB2 heterodimer activity
lapatinib
