Genetics: Cancer Genetics

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created 6 years ago by jgaversa5
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1

are oncogenes dominant or recessive

dominant

2

what do oncogene mutate to

proto=oncogenes

3

what do mutations in oncogenes do the protein function

makes excess protein

makes abnormal protein

gain of function

4

what is an example of an inherited oncogene form of cancer

activated RET

5

what type of mutation is activated RET

receptor tyrosine kinase

6

what type of cancer does activated RET predispose people to

multiple endocrine adenomatous type 2

7

how is RET transferred in terms of patterns of inheritance

AD

8

what type of particular cancers does RET predispose people to

medullary carcionma of the thyroid

9

what does medullary carcionma of the thyroid from RET mutation associate with

pheochromocytoma, benign parathyroid adenoma, or both

10

what are the types of mutations that can create activated oncogenes

point mutations
translocations

11

what is the common point mutation that leads to activated oncogenes

Ras-GTP mutation

12

what does the Ras-GTP mutation do for the Ras protein

locks it in GTP bound state

13

what are the well known translocation based cancers of activated oncogenes

CML
Burkitt's Lymphoma
Follicular B cell lymphoma

14

what is the CML mutation

ABL to BCR 9 to 22

15

what is the result of the CML mutation

makes chimeric protein with increased kinase activity

16

what is the Burkitt's lymphoma mutation

Myc to Ig enhancer from 8 to 14

17

what happens as a result of the mutation of Burkitt's lymphoma

overexpression of Myc in B cells

18

whatis the normal role of myc

transricption factor

19

what is the Follicular B cell lymphoma mutation

BCL2 to Ig enhancer from 18 to 14

20

what happens as a result of the mutation of follicular B cell lymphoma

BCL2 overexpression in B cells

21

what is the normal role of BCL2

antiapoptotic protein

22

what are the heritable forms of cancer

mendelian
multifactorial

23

what is included in a multifactorial cancer

genetic and environmental factors

24

what suggests an increased risk in multfactorial cancer

family history of cancer in multipe 1st and 2nd degree relatives

25

what happens when tumor suppressor genes are mutated (to the proteins themselves)

loss of function

26

are msot tumor suppressor genes cellularly dominant or recessive

recessive

27

what is the normal role of all tumor suppressor genes

reegulators

28

what are the types of tumor suppressor genes

gatekeepers
guardians

29

what do gatekeepers do in general for cells

regulate

30

what do guardians do in general fro ceslls

repair

31

how does familial Rb differ from sporadic

earlier age of onset and potential bilateral tumors

32

how is Rb inherited

AD

33

what hypothesis explains lots of familial cancers

two-hit hypothesis

34

what is the two hit hypothesis

individual inherits one mutatnt copy (hit 1) and somatic mutation occurs in one cell taht knocks out wild type function (hit 2)

35

what do most two-hit hypotheses result in

loss of heterozygosity

36

what does Rb carry an increased risk for

osteosarcoma, melanoma, soft tissue sarcoma, breast cancer

37

what type of protein is Rb

phosphoprotein

38

what phosphorylates Rb

CDK

39

what does Rb normally bind to

E2F

40

what characterizes Li Fraumeni syndrome

cancers in young people

41

how is Li Fraumeni syndrome inherited

AD

42

what is the mutation of note in Li Fraumeni syndrome

p53

43

why is not having p53 such a problem in Li Fraumeni syndrome

p53 normally institutes a check point to repair DNA damage OR induce apopotosis if damage is nor repaired

44

how is familial colon cancer inherited

AD

45

what is the main form of familial colon cancer

adenomatous polyposis coli

46

what happens to APC heterozygotes

get many adenomatous polyps and one or more becomes malignant; mutation or LOH of second copy

47

what is the mutation linked to FAP

APC

48

what does APC normally do

degrades cytoplasmic beta catenin

49

what is cytoplasmic beta catenin normally bound to prior to degradation

E-cadherin

50

what does beta catenin do if it is not bound to APC degradation

activates cell proliferative genes like myc

51

what is another familial colon cancer

HNPCC

52

what is the inheritance of HNPCC

AD

53

what are the gender differences assd with HNPCC

90% male risk

70% female risk, also 40% endometrial, 10-20% biliary tract, urinary tract, ovary

54

what is the mutation in HNPCC

MMR

55

what type of gene is MMR

caretaker (guardian) gene

56

what type of mutations does losing MMR in HNPCC open the body up to

ponit mutations and instability of simple sequence repeats

- multiple alleles of microsatelite polymorphism in single individual's tumor DNA

57

what is the increased breast cancer risk in someone with 1 first degree relative with it

3x

58

what is the increased breast cancer risk in someone with more than 1 first degree relative with it

10x

59

how does age of onset of first degree relative influence breat cancer risk

earlier, higher risk

60

what is the hereditary breast cancer gene

BRCA1/2

61

what are the functions of BRCA1 and 2

doublestrand break repair and homologous recominbation

62

what is an additional function of BRCA1

transcription coupled repair from UV light or oxidative damage

63

how are BRCA1/2 inherited

AD

64

does BRCA1 or 2 cause more breast cancer

1

65

how does BRCA1/2 breast cancers differ

2 later onset

66

does BRCA 1 or 2 have higher risk for carriers to develop cancer and what types

1: higher (breast)
2: lower but also ovarian risk high

67

what are the increased risk cancers for BRCA1

ovca
stomach, leukemia, prostate

68

what are the incrased risk cancers for BRCA2

male brca
prostate ca, panc ca

69

what is the CHK2 role and what does it do

G2 checkponit kinase

activates BRCA1

70

what does ATM do

activates CHK2

71

what do ATM homozygotes have

ataxia telangiectasia

72

what is BRIP1

BRCA1 interacting protein

73

what do BRIP1 homozygotes have

Fanconi's anemia

74

what is PALB2

partner and localizer of BRCA2

75

what do PALB2 homozygotes have

Fanconi's anemia

76

what does RAD51 do

transports BRCA2 to strand break

77

what is the Li Fraumeni mutation

p53

78

what is the Cowden syndrome mutation

PTEN

79

what is an autosomal recessive hereditary cancer

xeroderma pigmentosum

80

what is the phenotype of XP

hypersensitivity to light

81

what is early symptoms of XP

easy sunburn and photosensitivity, freckling

82

what are the late symptoms of XP

premature skin aging

83

what is the main problem in XP

excision repair pathway disruption

84

what is the most common mutated gene in cancer

p53

85

what is, besides p53, a common mutated gene in sporadic cancer

Rb1

86

what is often seen in sporadic breast cancers

one copy of BRCA 1 or 2

87

what are common mutations in sporadic colon cancers

MMR and APC

88

in 70% of those CRCs without FAP, what is present genetically

both APCs mutated in adenomatous polyps

89

in 30% of those CRCs without FAP, what is presnt genetically

mutations that block beta catenin phosphorylation

90

beides APC and beta catenin mutations, what are common mutations in sporadic CRC

KRAS and both p53 copies

91

why wouldn't you screen for BRCA1/2 mutations

just a fraction of cancers, also both loci show allelic heterogeneity and sequencing is expensive

environmental factors play a role too

92

what are some environmental factors with BRCA1/2

early menarche and/or late menopause
obesity
lack of physical exercise
high alcohol intake
diet

93

what are the screening criteria for BRCA 1/2

premenopausal onset of breast cancer,
bilateral breast cancer,
first degree relattive with ovca or brca,
multiple 2nd degree relatives with brca or ovca,
one relative with both primary ovca and brca,
ashkenzi jew with personal fhx of brca or ovca,
male brca

94

what are some complications of BRCA1/2 screening

incorrect interpretation

not all with positive will get cancer (incomplete penetrance)

negative test doesnt mean no risk

95

what are some ethical reasons not to screen for BRCA 1/2

prophylaxis drastic and still susceptible to other cancers

harm: insurance, career, kids/marriage

costs