Scott: Breast Cancer Genetics

Question 1

where does breast cancer arise from within normal tissue?

Answer 1

epithelial layer

Question 2

T or F: adult tissue contains stem and progenitor cells which provided capacity for growth throughout the lifespan?

Answer 2

true

Question 3

_____ mutation affects all cells in the body

Answer 3

germline mutations (err or sperm)

Question 4

____ mutation occurs in a cell in the body, only affects a single cell and its clonal descendants

Answer 4

somatic mutation

Question 5

is a somatic mutation passed down through life of the individual and onto its offspring?

Answer 5

NO. not to offspring, NOT a germline mutations

Question 6

inheritance of susceptibility (BRCA 1 and 2) is what type of inheritance pattern?

Answer 6

Autosomal dominant. inheritance of a single copy confers susceptibility

Question 7

what does BRCA1 and 2 actually DO?

Answer 7

essential components of homologous recombination arm of DNA repair machinery, which then allows for genomic instability creating conditions for oncogenic somatic mutations to arise

Question 8

in the _____ (absence or presence) of BRCA1, luminal progenitor cells accumulate

Answer 8

absence

Question 9

what percentage of breast cancers are sporadic?

Answer 9

90%

Question 10

subtypes differ in clinical characteristics: Luminal A has _____ (low, normal, high) levels of estrogen receptor, and therefore a _____ (worst, unchanging, best) prognosis?

Answer 10

HIGH. BEST.

Question 11

subtypes differ in clinical characteristics: _____ is the overexpression of HER2 and the prognosis is improved with ______

Answer 11

HER2-amplified. Trastuzamab

Question 12

subtypes differ in clinical characteristics: what type is often triple negative (NO ER, PR, no amp of HER2), BRCA mutations

Answer 12

BASAL-like

Question 13

what treatments are used to block ER signaling in treating ER+ breast cancer?

Answer 13

Selective estrogen receptor modulators, aromatase inhibitors

Question 14

ERalpha promotes transcription of secreted growth factor, such as _____

Answer 14

amphiregulin

Question 15

extracellular estrogen controls proliferation of luminal cells _____ (direct/indirect)

Answer 15

INDIRECtly

Question 16

tumor cells estrogen regulates growth _____ (direct/indirectly)

Answer 16

directly

Question 17

How are tumor cells different than normal cells?

Answer 17

increase in # of cells expressing ER. change in which genes are regulated by ER binding

Question 18

how are tumor cells NOT different than normal cells?

Answer 18

no mutations or amplifications of genes encoding estrogen or RE

Question 19

how does ER promote transcription of a different set of genes in breast cancer?

Answer 19

overexpression of the pioneer transcription factor FOXA1

Question 20

how does FOXA1 work?

Answer 20

it allows BINDING OF CLOSED chromatin at select sites and opens it and allows access to ER binding!!!!

Question 21

what is one of the sites opened by FOXA1?

Answer 21

CYCLIN D1 promoter (therefore dysregulates proliferation)

Question 22

what was the first SERM used to block E2/Er signaling in breast cancer?

Answer 22

Tamoxifen

Question 23

________ type of drugs block synthesis of estrogen in non-ovarian tissues

Answer 23

Aromatase inhibitors. they DO NOT AFFECT THE ESTROGEN RECEPTOR

Question 24

T or F: ERBB2 does require ligand binding for activation

Answer 24

FALSE. DOES NOT. increased ERBB2 expression, due to amplification allows dimerization to occur by mass action.

Question 25

____ is a monoclonal antibody that binds extracellular domain of ERBB2 and blocks activity of its homodimers

Answer 25

Trastuzumab

Question 26

____ is a small molecule inhibitor which binds and blocks kinase active site and blocks the EGFR-ERBB2 heterodimer activity

Answer 26

lapatinib