Cancer Flashcards
1
Q
Where do carcinomas originate?
A
Epithelial tissues
2
Q
Where do adenocarcinomas originate?
A
Glandular or secretory cells
3
Q
What are sarcomas?
A
Rare solid tumors in connective tissues
4
Q
Where do sarcomas originate?
A
Mesenchyme
5
Q
What are the top two cancers affecting males?
A
Non-melanoma skin cancer, and prostate respectively
6
Q
What are the top two cancers affecting women?
A
Breast and NMSCs
7
Q
Which cancer has the highest mortality rate associated with it?
A
Lung cancer
8
Q
Why are oncogenes important in cancers?
A
If altered for abnormal stimulation they result in abnormal cell proliferation
9
Q
Mutations in oncogenes are what type of mutations?
A
GOF
10
Q
How many mutations does a GOF mutation like in an oncogene require? And what is usually involved in these GOF mutations of oncogenes?
A
Only require one mutation, involves GFs, receptors, TFs in growth pathways and anti-apoptotic proteins
11
Q
What type of mutation are tumor suppressors classified as?
A
LOF
12
Q
What things are involved in these LOF mutations?
A
Cells that normally control/block cell growth and proliferation
13
Q
How many mutations must occur to affect tumor suppressor genes?
A
2 mutations
14
Q
The majority of cancer in humans is?
A
Carcinomas
15
Q
What is P53?
A
A tumor suppressor
16
Q
What is P53 usually bound to?
A
Mdm2
17
Q
What causes P53 to unbind from mdm2?
A
DNA damage or cell abnormalities leading to cell cycle arrest in G1-S phase
18
Q
What is another cell cycle regulator similar to p53
A
Rb
19
Q
What is Rb?
A
A phosphoprotein that activates e2f after phosphorylation
20
Q
What happens when Rb is hypophosphorylated
A
It inhibits g1-s
21
Q
What is the result of a mutation in Rb?
A
Often causes retinoblastoma or can contribute to oncogenesis
22
Q
What is oncogenesis
A
When proto-oncogenes are activated to oncogenes then they activate anti-apoptotic genes
23
Q
A tumor is referred to cancerous when?
A
When it is malignant
24
Q
What makes a tumor malignant
A
When it loses attachment to basal layer and has invasive properties with or without metastasis
25
When is a benign tumor an issue?
When the shear bulk of it becomes an issue or causes hypersecretion (in the brain, hormones, Cushings disease)
26
What are the effects of CYP450 and benzo-a-pyrene in terms of carcinogens
Indirect or procarcinogens are converted to a reactive species that can interact and damage DNA
27
How does CYP450 affect aflatoxin?
It converts it aflatoxin Bq into epoxide which can intercalate with DNA (liver cancer) and forms adduct
28
Describe the effects of benzo-a-pyrene (cigarette smoke)
It is converted to BPDE which can form an adduct
29
Some examples of DNA damage that leads to malignant transformations in DNA are?
Uv radiation (T-T dimers in XP), alkylation, chemical cross-linking
30
HPV's viral oncogenes inactivate p53 and Rb , what are these oncogenes?
E6 and E7
31
This present autosomal dominant inheritance that affects two or more endocrine glands. There's a GOF in RET. What is the syndrome and what is the problem?
Multiple endocrine neoplasia type 2 (MEN2). Receptor tyrosine kinase mutation causes it to be constitutively active
32
What if you have a mutation in MET (HGFR), what are you thinking?
Hereditary papillary renal carcinoma, this mutation causes constitutively active leading to tumor growth, angiogenesis and metastasis
33
What is RTK normally involved in?
Wound healing and embryonic development
34
Burkitt lymphoma, where is the translocation and what is the mechanism?
8:14 translocation, this leads to overexpression of MYC on chr 8 is translocated to distal Ig heavy chain promoter on chr 14. MYC is now under control of Ig promoter
35
Over expression of anti-apoptotic bcl2 due to a translocation between chr 14:18. Bcl2 is now under control of chr 18's Ig heavy chain promoter. What cancer are you thinking?
Follicular lymphoma
36
Describe chronic myelogenous leukemia (CML)
BCR and ABL fuse to constitutively activate intracellular tyrosine kinase activity, this is known as Philadelphia chromosome, leading to increased cell growth and decreased apoptosis. Translocation between 9:22
37
Individuals with translocation between chr 9:22 will present with massive splenomegaly, how do we treat this?
Imantinib/Gleevec (BCR-ABL tyrosine kinase inhibitor), bone marrow transplant is curative
38
Translocation between 15:17 and leads to a fusion of PML-RAR alpha, which is a nuclear receptor and a transcription factor allowing for differentiation of WBCs. The fusion of these proteins reveals GOF rearrangements and promotes proliferation and suppresses myeloid differentiation. What cancer is this?
Acute promyelocytic leukemia (APL)
39
What is PML
A transcription factor that blocks cell proliferation and induces apoptosis (tumor suppressor)
40
What is Ewing sarcoma?
Translocation of 11:22 leading to fusion of EWS-FLI1 (small round tumors of bone and soft tissue) affecting mostly young males. activation of TF LFI1
41
Amplification of N-MYC is seen in what?
Neuroblastomas
42
What is P53?
A tumor suppressor
43
What is P53 usually bound to?
Mdm2
44
What causes P53 to unbind from mdm2?
DNA damage or cell abnormalities leading to cell cycle arrest in G1-S phase
45
What is another cell cycle regulator similar to p53
Rb
46
What is Rb?
A phosphoprotein that activates e2f after phosphorylation
47
What happens when Rb is hypophosphorylated
It inhibits g1-s
48
What is the result of a mutation in Rb?
Often causes retinoblastoma or can contribute to oncogenesis
49
What is oncogenesis
When proto-oncogenes are activated to oncogenes then they activate anti-apoptotic genes
50
A tumor is referred to cancerous when?
When it is malignant
51
What makes a tumor malignant
When it loses attachment to basal layer and has invasive properties with or without metastasis
52
When is a benign tumor an issue?
When the shear bulk of it becomes an issue or causes hypersecretion (in the brain, hormones, Cushings disease)
53
What are the effects of CYP450 and benzo-a-pyrene in terms of carcinogens
Indirect or procarcinogens are converted to a reactive species that can interact and damage DNA
54
How does CYP450 affect aflatoxin?
It converts it aflatoxin Bq into epoxide which can intercalate with DNA (liver cancer) and forms adduct
55
Describe the effects of benzo-a-pyrene (cigarette smoke)
It is converted to BPDE which can form an adduct
56
Some examples of DNA damage that leads to malignant transformations in DNA are?
Uv radiation (T-T dimers in XP), alkylation, chemical cross-linking
57
HPV's viral oncogenes inactivate p53 and Rb , what are these oncogenes?
E6 and E7
58
This present autosomal dominant inheritance that affects two or more endocrine glands. There's a GOF in RET. What is the syndrome and what is the problem?
Multiple endocrine neoplasia type 2 (MEN2). Receptor tyrosine kinase mutation causes it to be constitutively active
59
What if you have a mutation in MET (HGFR), what are you thinking?
Hereditary papillary renal carcinoma, this mutation causes constitutively active leading to tumor growth, angiogenesis and metastasis
60
What is RTK normally involved in?
Wound healing and embryonic development
61
Burkitt lymphoma, where is the translocation and what is the mechanism?
8:14 translocation, this leads to overexpression of MYC on chr 8 is translocated to distal Ig heavy chain promoter on chr 14. MYC is now under control of Ig promoter
62
Over expression of anti-apoptotic bcl2 due to a translocation between chr 14:18. Bcl2 is now under control of chr 18's Ig heavy chain promoter. What cancer are you thinking?
Follicular lymphoma
63
Describe chronic myelogenous leukemia (CML)
BCR and ABL fuse to constitutively activate intracellular tyrosine kinase activity, this is known as Philadelphia chromosome, leading to increased cell growth and decreased apoptosis. Translocation between 9:22
64
Individuals with translocation between chr 9:22 will present with massive splenomegaly, how do we treat this?
Imantinib/Gleevec (BCR-ABL tyrosine kinase inhibitor), bone marrow transplant is curative
65
Translocation between 15:17 and leads to a fusion of PML-RAR alpha, which is a nuclear receptor and a transcription factor allowing for differentiation of WBCs. The fusion of these proteins reveals GOF rearrangements and promotes proliferation and suppresses myeloid differentiation. What cancer is this?
Acute promyelocytic leukemia (APL)
66
What is PML
A transcription factor that blocks cell proliferation and induces apoptosis (tumor suppressor)
67
What is P53?
A tumor suppressor
68
What is P53 usually bound to?
Mdm2
69
What causes P53 to unbind from mdm2?
DNA damage or cell abnormalities leading to cell cycle arrest in G1-S phase
70
What is another cell cycle regulator similar to p53
Rb
71
What is Rb?
A phosphoprotein that activates e2f after phosphorylation
72
What happens when Rb is hypophosphorylated
It inhibits g1-s
73
What is the result of a mutation in Rb?
Often causes retinoblastoma or can contribute to oncogenesis
74
What is oncogenesis
When proto-oncogenes are activated to oncogenes then they activate anti-apoptotic genes
75
A tumor is referred to cancerous when?
When it is malignant
76
What makes a tumor malignant
When it loses attachment to basal layer and has invasive properties with or without metastasis
77
When is a benign tumor an issue?
When the shear bulk of it becomes an issue or causes hypersecretion (in the brain, hormones, Cushings disease)
78
What are the effects of CYP450 and benzo-a-pyrene in terms of carcinogens
Indirect or procarcinogens are converted to a reactive species that can interact and damage DNA
79
How does CYP450 affect aflatoxin?
It converts it aflatoxin Bq into epoxide which can intercalate with DNA (liver cancer) and forms adduct
80
Describe the effects of benzo-a-pyrene (cigarette smoke)
It is converted to BPDE which can form an adduct
81
Some examples of DNA damage that leads to malignant transformations in DNA are?
Uv radiation (T-T dimers in XP), alkylation, chemical cross-linking
82
HPV's viral oncogenes inactivate p53 and Rb , what are these oncogenes?
E6 and E7
83
This present autosomal dominant inheritance that affects two or more endocrine glands. There's a GOF in RET. What is the syndrome and what is the problem?
Multiple endocrine neoplasia type 2 (MEN2). Receptor tyrosine kinase mutation causes it to be constitutively active
84
What if you have a mutation in MET (HGFR), what are you thinking?
Hereditary papillary renal carcinoma, this mutation causes constitutively active leading to tumor growth, angiogenesis and metastasis
85
What is RTK normally involved in?
Wound healing and embryonic development
86
Burkitt lymphoma, where is the translocation and what is the mechanism?
8:14 translocation, this leads to overexpression of MYC on chr 8 is translocated to distal Ig heavy chain promoter on chr 14. MYC is now under control of Ig promoter
87
Over expression of anti-apoptotic bcl2 due to a translocation between chr 14:18. Bcl2 is now under control of chr 18's Ig heavy chain promoter. What cancer are you thinking?
Follicular lymphoma
88
Describe chronic myelogenous leukemia (CML)
BCR and ABL fuse to constitutively activate intracellular tyrosine kinase activity, this is known as Philadelphia chromosome, leading to increased cell growth and decreased apoptosis. Translocation between 9:22
89
Individuals with translocation between chr 9:22 will present with massive splenomegaly, how do we treat this?
Imantinib/Gleevec (BCR-ABL tyrosine kinase inhibitor), bone marrow transplant is curative
90
Translocation between 15:17 and leads to a fusion of PML-RAR alpha, which is a nuclear receptor and a transcription factor allowing for differentiation of WBCs. The fusion of these proteins reveals GOF rearrangements and promotes proliferation and suppresses myeloid differentiation. What cancer is this?
Acute promyelocytic leukemia (APL)
91
What is PML
A transcription factor that blocks cell proliferation and induces apoptosis (tumor suppressor)
