Breast Cancer Study Flashcards Preview

PATHOLOGY > Breast Cancer Study > Flashcards

Flashcards in Breast Cancer Study Deck (36):
1

Inherited cancer

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

2

Sporadic

no inheritance pattern; caused by environmental issues

3

Oncogenes

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

4

Oncogene - point mutation

RAS -- abnormal protein

5

RAS point mutation may result in

bladder, lung, colon, or pancreas cancer

6

Oncogene - gene amplification

Myc -- over expression of Myc that controls proliferation

7

Myc gene amplification may result in

Breast, ovary, pancreas, lung, and esophagus cancer

8

Oncogene - chromosomal translocation

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

9

CML chromosome translocation may result in

Chronic myelogenous leukemia (CML)

10

Oncogene - DNA rearrangements

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

11

Oncogene - insertional mutagenesis

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

12

Viral conversion (insertional mutagenesis) can result from

EBE, HCV, HPV, HTL-1, KSHV

13

TRK DNA rearrangement may cause

hereditary colon cancer

14

Retinoblastoma

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

15

LOF of Retinoblastoma causes

hereditary retinoblastoma

16

Why is a sporadic tumor rarely caused by tumor suppressor genes

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

17

p53

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

18

BRCA-1 -2

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

19

Gene mutations seen in both hereditary and non-hereditary

RB and p53 (gatekeepers)

20

Gene mutations seen primarily in hereditary tumors

BRCA1,2 (caretakers)

21

Repairing dsDNA breaks

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

22

Homologous recombination of dsDNA breaks

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

23

Non-homologous end joining

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

24

Gain of function mutations

mutations produce proteins with new or excessive activity; MENII

25

Multiple endocrine neoplasia type II (MEN-II)

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

26

MEN-II is associated with the inheritance of

a single RET gene (TKR)

27

Breast cancer risk factors

environment- hormones, lifestyle (exercise, smoking)

28

Penetrance

# of carriers who develop the disease

29

BRCA1-2 penetrance

30-90%

30

BRCA1 is associated with

ovarian cancer

31

BRCA2 is associated with

ovary cancer, male breast cancer

32

BRCA1 and 2 associated with

epithelial and pancreatic cancer

33

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

34

2009: BRCA-2 variant I2527F results in

confirmed protein function disruption and connection to CA established

35

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

36

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

85%, median age onset 20y/o