Breast Cancer Study Flashcards
Inherited cancer
inherited mutations increase the RISK of developing cancer, events after birth will trigger the cancer development
Sporadic
no inheritance pattern; caused by environmental issues
Oncogenes
class of genes whose presence initiates the development of cancer by excessive proliferation
Oncogene - point mutation
RAS – abnormal protein
RAS point mutation may result in
bladder, lung, colon, or pancreas cancer
Oncogene - gene amplification
Myc – over expression of Myc that controls proliferation
Myc gene amplification may result in
Breast, ovary, pancreas, lung, and esophagus cancer
Oncogene - chromosomal translocation
CML – breakage on chromsome 9 and 22 ends are switched –> production of abnormal fusion protein, over expression of CML
CML chromosome translocation may result in
Chronic myelogenous leukemia (CML)
Oncogene - DNA rearrangements
TRK – rearrangement -> fusion protein -> codes for GF -> stimulated cellular activity
Oncogene - insertional mutagenesis
Avian leukosis virus inserts LTRs next to Myc -> overproduction of normal cellular protein
Viral conversion (insertional mutagenesis) can result from
EBE, HCV, HPV, HTL-1, KSHV
TRK DNA rearrangement may cause
hereditary colon cancer
Retinoblastoma
loss of function (allows cells to pass into S phase without phosphorylation from GFs) TUMOR-SUPPRESSOR
LOF of Retinoblastoma causes
hereditary retinoblastoma
Why is a sporadic tumor rarely caused by tumor suppressor genes
because without hereditary influence, 2 mutations must spontaneously arise to k/o gene
p53
role in preventing cell cycle progression when DNA damage is present, mutation allows aberrant cell cycle progression TUMOR-SUPPRESSOR
BRCA-1 -2
repair DNA damage, mutations have impaired DNA repair –> subsequent mutation –> cancer
Gene mutations seen in both hereditary and non-hereditary
RB and p53 (gatekeepers)
Gene mutations seen primarily in hereditary tumors
BRCA1,2 (caretakers)
Repairing dsDNA breaks
is more difficult than ssDNA breaks, because there is no template
Homologous recombination of dsDNA breaks
use of the homologous chromosome as a template to repair the broken chromosome; BRCA-1,2, ATM kinase -> repair
Non-homologous end joining
broken fragments are ligated in any way, rearranged, translocated, etc -> instability
Gain of function mutations
mutations produce proteins with new or excessive activity; MENII
Multiple endocrine neoplasia type II (MEN-II)
developmental abnormalities associated with benign and malignant tumors of the endocrine glands
MEN-II is associated with the inheritance of
a single RET gene (TKR)
Breast cancer risk factors
environment- hormones, lifestyle (exercise, smoking)
Penetrance
of carriers who develop the disease
BRCA1-2 penetrance
30-90%
BRCA1 is associated with
ovarian cancer
BRCA2 is associated with
ovary cancer, male breast cancer
BRCA1 and 2 associated with
epithelial and pancreatic cancer
2008: BRCA-2 variant I2527F results in
substitution of phenylalanine for isoleucine, may or may not affect the function of the protein, cannot establish link to CA
2009: BRCA-2 variant I2527F results in
confirmed protein function disruption and connection to CA established
Probability of breast cancer associated with a mutation in BRCA1-2 increases if
Multiple 1st degree relatives affected, individuals affected before menopause, 1st degree relative with male breast cancer or 1st degree relative with ovarian cancer
lifetime breast cancer risk in women with germ line mutations of BRCA1-2 is
85%, median age onset 20y/o
