Breast Cancer Study

Question 1

Inherited cancer

Answer 1

inherited mutations increase the RISK of developing cancer, events after birth will trigger the cancer development

Question 2

Sporadic

Answer 2

no inheritance pattern; caused by environmental issues

Question 3

Oncogenes

Answer 3

class of genes whose presence initiates the development of cancer by excessive proliferation

Question 4

Oncogene - point mutation

Answer 4

RAS – abnormal protein

Question 5

RAS point mutation may result in

Answer 5

bladder, lung, colon, or pancreas cancer

Question 6

Oncogene - gene amplification

Answer 6

Myc – over expression of Myc that controls proliferation

Question 7

Myc gene amplification may result in

Answer 7

Breast, ovary, pancreas, lung, and esophagus cancer

Question 8

Oncogene - chromosomal translocation

Answer 8

CML – breakage on chromsome 9 and 22 ends are switched –> production of abnormal fusion protein, over expression of CML

Question 9

CML chromosome translocation may result in

Answer 9

Chronic myelogenous leukemia (CML)

Question 10

Oncogene - DNA rearrangements

Answer 10

TRK – rearrangement -> fusion protein -> codes for GF -> stimulated cellular activity

Question 11

Oncogene - insertional mutagenesis

Answer 11

Avian leukosis virus inserts LTRs next to Myc -> overproduction of normal cellular protein

Question 12

Viral conversion (insertional mutagenesis) can result from

Answer 12

EBE, HCV, HPV, HTL-1, KSHV

Question 13

TRK DNA rearrangement may cause

Answer 13

hereditary colon cancer

Question 14

Retinoblastoma

Answer 14

loss of function (allows cells to pass into S phase without phosphorylation from GFs) TUMOR-SUPPRESSOR

Question 15

LOF of Retinoblastoma causes

Answer 15

hereditary retinoblastoma

Question 16

Why is a sporadic tumor rarely caused by tumor suppressor genes

Answer 16

because without hereditary influence, 2 mutations must spontaneously arise to k/o gene

Question 17

p53

Answer 17

role in preventing cell cycle progression when DNA damage is present, mutation allows aberrant cell cycle progression TUMOR-SUPPRESSOR

Question 18

BRCA-1 -2

Answer 18

repair DNA damage, mutations have impaired DNA repair –> subsequent mutation –> cancer

Question 19

Gene mutations seen in both hereditary and non-hereditary

Answer 19

RB and p53 (gatekeepers)

Question 20

Gene mutations seen primarily in hereditary tumors

Answer 20

BRCA1,2 (caretakers)

Question 21

Repairing dsDNA breaks

Answer 21

is more difficult than ssDNA breaks, because there is no template

Question 22

Homologous recombination of dsDNA breaks

Answer 22

use of the homologous chromosome as a template to repair the broken chromosome; BRCA-1,2, ATM kinase -> repair

Question 23

Non-homologous end joining

Answer 23

broken fragments are ligated in any way, rearranged, translocated, etc -> instability

Question 24

Gain of function mutations

Answer 24

mutations produce proteins with new or excessive activity; MENII

Question 25

Multiple endocrine neoplasia type II (MEN-II)

Answer 25

developmental abnormalities associated with benign and malignant tumors of the endocrine glands

Question 26

MEN-II is associated with the inheritance of

Answer 26

a single RET gene (TKR)

Question 27

Breast cancer risk factors

Answer 27

environment- hormones, lifestyle (exercise, smoking)

Question 28

Penetrance

Answer 28

of carriers who develop the disease

Question 29

BRCA1-2 penetrance

Answer 29

30-90%

Question 30

BRCA1 is associated with

Answer 30

ovarian cancer

Question 31

BRCA2 is associated with

Answer 31

ovary cancer, male breast cancer

Question 32

BRCA1 and 2 associated with

Answer 32

epithelial and pancreatic cancer

Question 33

2008: BRCA-2 variant I2527F results in

Answer 33

substitution of phenylalanine for isoleucine, may or may not affect the function of the protein, cannot establish link to CA

Question 34

2009: BRCA-2 variant I2527F results in

Answer 34

confirmed protein function disruption and connection to CA established

Question 35

Probability of breast cancer associated with a mutation in BRCA1-2 increases if

Answer 35

Multiple 1st degree relatives affected, individuals affected before menopause, 1st degree relative with male breast cancer or 1st degree relative with ovarian cancer

Question 36

lifetime breast cancer risk in women with germ line mutations of BRCA1-2 is

Answer 36

85%, median age onset 20y/o