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Flashcards in CH3 - Principles of Neoplasia Deck (169)
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91

KIT

Stem cell growth factor receptor, Point mutation, Gastrointestinal stromal tumor

92

RAS gene family

GTP-binding protein, Point mutation, Carcinomas, melanoma, and lymphoma

93

ABL

Tyrosine kinase T(9;22) with BCR CML and some types of ALL

94

What are the nuclear regulators?

C-MYC, N-MYC, L-MYC

95

c-MYC

Transcription factor, t(8;I4) involving IgH, Burkitt lymphoma

96

N-MYC

Transcription factor, Amplification, Neuroblastoma

97

L-MYC

Transcription factor, Amplification, Lung carcinoma (small cell)

98

CCND1 (cyclin D1)

Cyclin t(8;14) involving IgH, Mantle cell lymphoma

99

If DNA repair is not possible, what does p53 do?

induces apoptosis.

100

How does p53 induce apoptosis?

upregulates BAX, which disrupts Bcl2 leading to cytochrome c leaks from the mitochondria activating apoptosis

101

Knudson two-hit hypothesis

both copies of the p53 gene must be knocked out for tumor formation, Both copies of Rb gene must be knocked out for tumor formation

102

Loss of p53 is seen in what percentage of cancers?

>50% of cancers.

103

p53 Germline mutation results in

Li-Fraumeni syndrome (2nd hit is somatic),

104

Li-Fraumeni syndrome is characterized by?

the propensity to develop multiple types of carcinomas and sarcomas,

105

Rb

regulates progression from G0 to S phase.

106

How does Rb regulate the progression to S phase?

holds the E2F transcription factor, which is necessary for transition to the S phase

107

E2F is released when?

RB is phosphorylated by the cyclinD/cyclin-dependent kinase 4 (CDK4) complex

108

Rb mutation results in

constitutively free E2F, allowing progression through the cell cycle and uncontrolled growth of cells.

109

Sporadic mutation

(both hits are somatic) and it is characterized by unilateral retinoblastoma

110

Rb Germline mutation results in

familial retinoblastoma (2nd hit is somatic) and is characterized by bilateral retinoblastoma and osteosarcoma.

111

What is the function of regulators of apoptosis?

Prevent apoptosis in normal cells, but promote apoptosis in mutated cells whose DNA cannot be repaired (e.g Bcl2)

112

Bcl2

normally stabilizes the mitochondrial membrane, blocking release of cytochrome c

113

Disruption of Bcl2 allows what to happen?

Cytochrome c to leave the mitochondria and activate apoptosis

114

Bcl2 in follicular lymphoma?

it is overexpressed in follicular lymphoma,

115

Why is Bcl2 overexpressed in follicular lymphoma?

t(14;18) moves Bcl2 (chromosome 18) to the Ig heavy chain locus (chromosome 14), resulting in increased Bcl2.

116

How is apoptosis inhibited in follicular lymphoma?

Mitochondrial membrane is further stabilized by overexpressed Bcl2, prohibiting apoptosis.

117

In follicular lymphoma, how does the inhibition of apoptosis lead to lymphoma?

B cells that would normally undergo apoptosis during somatic hypermutation in the lymph node germinal center accumulate, leading to lymphoma.

118

What is necessary for cell immortality?

Telomerase

119

Normally telomeres do what?

shorten with serial cell divisions, eventually resulting in cellular senescence

120

What is the relationship between cancers and telomerase?

cancers often have up regulated telomerase, which preserves telomeres