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Kathleen's Renal I > deck_3805474 > Flashcards

Flashcards in deck_3805474 Deck (81):
1

A mutation in the proto-oncogene ERBB1  (EGFR) creates what?

Adenocarcinoma of the lung  - mutation activation

2

A mutation in the proto-oncogene ERRB2 (HER) creates what?

Breast carcinoma - amplification mode of activation

3

A mutation in the proto-oncogene RET creates what?

multiple endocrine neoplasia 2A and BFamilial medullary thyroid carcinomas

4

A mutation in the proto-oncogene PDGFRB  creates what?

Gliomas & leukemias Overexpression and translocation mode of activation

5

A mutation in the proto-oncogene KIT creates what?

Gastrointestinal stromal tumors - seminomas, certain leukemias Point mutation mode of activation

6

A mutation in the proto-oncogene ALK creates what?

Adenocarcinoma of the lung - certain lymphomas, neuroblastoma Translocation, fusion gene mode of activation

7

A mutation in the proto-oncogene KRAS creates what?

Colon, lung and pancreatic tumors - activated via a point mutation

8

A mutation in the proto-oncogene NRAS creates what?

Melanomas, hematologic malignancies

9

A mutation in the proto-oncogene GNAS creates what?

pituitary adenoma, other endocrine tumors  - activation via a point mutation

10

A mutation in the proto-oncogene BRAF creates what?

Melanomas - also leukemias, colon carcinoma, etc. BRAF is a RAS signal transduction

11

A mutation in the proto-oncogene ABL creates what?

Chronic myeloid leukemia, acute lymphoblastic leukemia  - activated via a translocation, or a point mutation

12

A mutation in the proto-oncogene C-MYC creates what?

Burkitt Lymphoma - via translocation activation

13

A mutation in the proto-oncogene N-MYC creates what?

Neuroblastoma - small cell carcinoma of the lung - activated via an amplification

14

A mutation in the proto-oncogene L-MYC creates what?

Small-cell carcinoma of the lung - activated via amplification

15

A mutation in the proto-oncogene CCND1  (Cyclin D) creates what?

Mantle cell lymphoma - also multiple myeloma - activation via a translocation mechanism Breast and esophageal cancers too - activation via an amplification mechanism

16

A mutation in PAX8 gene can make it act like a proto-oncogene and cause what?

Renal carcinoma

17

A mutation in PAX5 gene can make it act like a proto-oncogene and cause what?

Non-Hodgkin LymphomaLymphocytic leukemia

18

A mutation in PAX3 and PAX7 genes can make it act like a proto-oncogene and cause what?

Embryonic rhabdomyosarcoma

19

Chronic myelogenous leukemia is caused by translocation activation of what genes?

ABL 9q34/BCR 22q11

20

Acute myeloid leukemia is caused by which translocation activation of what genes?

AML1 8q22/ETO 21q22**PML 15q22/RARA 17q12**

21

Burkitt Lymphoma is caused by translocation activation of what genes?

c-MYC 8q24IGH 14q32

22

Mantle cell lymphoma is caused by translocation activation of what genes?

CCND1 11q13IGH 14q32

23

Follicular lymphoma is caused by translocation activation of what genes?

IGH 14q32BCL2 18q21

24

Ewing sarcoma is caused by translocation activation of what genes?

FLI1 11q24EWSR1 22q12

25

Prostatic adenocarcinoma is caused by translocation activation of what genes?

TMPRSS2 (21q22.3)ETV1 (7p21.2)ETV4 (17q21)

26

What is the function of cyclines?

CDK4; D cyclins Form a complex that phosphorylates RB, allowing the cell to progress through the G1 restriction point

27

What is the function of the ARF family of genes?

INK4/ARF family (CDKN2A-C) p16/INK4a binds to cyclin D-CDK4 and promotes the inhibitory effects of RBp14/ARF increases p53 levels by inhibiting MDM2 activity

28

What is the function of RB?

Cell Cycle checkpoint component Tumor suppressive “pocket” protein that binds E2F transcription factors in its hypophosphorylated state, preventing G1/S transition; also interacts with several transcription factors that regulate differentiation 

29

What is the function of p53?

Cell Cycle Checkpoint component Tumor suppressor altered in the majority of cancers; causes cell cycle arrest and apoptosis. Acts mainly through p21 to cause cell cycle arrest. Causes apoptosis by inducing the transcription of pro-apoptotic genes such as BAX. Levels of p53 are negatively regulated by MDM2 through a feedback loop. p53 is required for the G1/S checkpoint and is a main component of the G2/M checkpoint.

30

What is the NF1 gene?

Tumor suppressor geneProtein: Neurofibromin-1Function: Inhibitor of RAS/MAPK signalingFamilial Syndrome: Neurofibromatosis type 1 (neurofibromas and malignant peripheral nerve sheath tumors) - i.e. skin lesionsSpecific Cancers: Neuroblastoma, juvenile myeloid leukemia

31

What is the NF2 gene?

Tumor Suppressor GeneProtein: Neurofibromin-2/merlinFunction: Cytoskeletal stability, Hippo pathway signalingFamilial Syndromes: Neurofibromatosis type 2 (acoustic schwannoma and meningioma)Sporadic Cancers: Schwannoma, meningioma (leads to hearing loss and brain tumors, not skin lesions)

32

What is the PTEN gene significant for?

Tumor Suppressor GeneProtein: Phosphatase and tensin homologueFunction: Inhibitor of PI3K/AKT signalingFamilial Syndromes: Cowden syndrome (variety of benign skin, GI, and CNS growths; breast, endometrial, and thyroid carcinoma)Sporadic Cancers: Diverse cancers, particularly carcinomas and lymphoid tumors

33

What is the RB gene significant for?

Tumor Suppressor Gene Protein: Retinoblastoma (RB) proteinFunction: Inhibitor of G1/S transition during cell cycle progressionFamilial Syndromes: Familial retinoblastoma syndrome (retinoblastoma, osteosarcoma, other sarcomas)Sporadic Cancers: Retinoblastoma; osteosarcoma carcinomas of breast, colon, lung

34

What is the gene VHL significant for?

Tumor Suppressor Gene Protein: Von Hippel Lindau (VHL) proteinFunction: Inhibitor of hypoxia-induced transcription factors (e.g., HIF1α)Familial Syndromes: Von Hippel Lindau syndrome (cerebellar hemangioblastoma, retinal angioma, renal cell carcinoma)Sporadic Cancers: Renal cell carcinoma

35

What is the gene TP53 significant for?

Tumor Suppressor Gene Protein: p53 proteinFunction: Cell cycle arrest and apoptosis in response to DNA damageFamilial Syndromes: Li-Fraumeni syndrome (diverse cancers)Sporadic Cancers: Most human cancers

36

What are the genes BRCA1, BRCA2 significant for?

Tumor Suppressor Genes protein: Breast cancer-1 and breast cancer-2 (BRCA1 and BRCA2function: Repair of double-stranded breaks in DNAfamilial syndromes: Familial breast and ovarian carcinoma; carcinomas of male breast; chronic lymphocytic leukemia (BRCA2)sporadic cancers: rare

37

What is the gene WT1 significant for?

Tumor Suppressor Gene Protein: Wilms tumor-1 (WT1)Function: Transcription factorFamilial Syndromes: Familial Wilms tumorSporadic Cancers: Wilms tumor, certain leukemias

38

What is the gene MEN1 significant for?

Tumor Suppressor Gene Protein: MeninFunction: Transcription factorFamilial Syndromes: Multiple endocrine neoplasia-1 (MEN1; pituitary, parathyroid, and pancreatic endocrine tumors) Sporadic Cancers: Pituitary, parathyroid, and pancreatic endocrine tumors

39

What is the major form of underlying cancer and causal mechanism for Cushing Syndrome  as a paraneoplastic syndrome?

Small-cell carcinoma of lungPancreatic carcinomaNeural tumors Mechanism: ACTH or ACTH-like substance

40

What is the major form of underlying cancer and causal mechanism for SIADH as a paraneoplastic syndrome?

Small-cell carcinoma of lung; Intracranial neoplasms Mechanism: Antidiuretic hormone or atrial natriuretic hormones

41

What is the major form of underlying cancer and causal mechanism for hypercalcemia as a paraneoplastic syndrome?

Squamous cell carcinoma of lungBreast carcinomaRenal carcinomaAdult T-cell leukemia/lymphoma Mechanism: Parathyroid hormone-related protein (PTHRP), TGF-α, TNF, IL-1

42

What is the major form of underlying cancer and causal mechanism for hypoglycemia as a paraneoplastic syndrome?

Ovarian carcinomaFibrosarcomaOther mesenchymal sarcomas Mechanism: Insulin or insulin-like substance

43

What is the major form of underlying cancer and causal mechanism for polycythemia as a paraneoplastic syndrome?

Gastric carcinomaRenal carcinomaCerebellar hemangiomaHepatocellular carcinoma Mechanism: Erythropoietin

44

What is the major form of underlying cancer and causal mechanism for carcinoid syndrome as a paraneoplastic syndrome?

Hepatocellular carcinomaBronchial adenoma (carcinoid)Pancreatic carcinomaMechanism: Serotonin, bradykinin

45

What is the major form of underlying cancer and causal mechanism for myasthenia gravis as a paraneoplastic syndrome?

Bronchogenic carcinomaThymic neoplasms Mechanism: Immunological

46

What is the major form of underlying cancer and causal mechanism for acanthosis nigricans as a paraneoplastic syndrome?

Gastric carcinomaLung carcinomaUterine carcinoma Mechanism: Immunological; secretion of epidermal growth factor

47

What is the major form of underlying cancer and causal mechanism for dermatomyositis as a paraneoplastic syndrome?

BronchogenicBreast carcinoma Mechansim: Immunological - look for heliotropic rash, mm weakness

48

What is the major form of underlying cancer and causal mechanism for Trousseau syndrome as a paraneoplastic syndrome?

  Venous thrombosis (Trousseau phenomenon) Pancreatic carcinomaBronchogenic carcinomaOther cancers Mechanism: Tumor products (mucins that activate clotting)

49

What is the major form of underlying cancer and causal mechanism for DIC as a paraneoplastic syndrome?

Acute promyelocytic leukemiaProstatic carcinoma Mechanism: Tumor products that activate clotting

50

What is the major form of underlying cancer and causal mechanism for nonbacterial thrombotic endocarditis as a paraneoplastic syndrome?

Advanced cancers Mechanism: Hypercoagulability

51

What are some direct-acting carcinogens?

Alkylating Agents  β-Propiolactone  Dimethyl sulfate  Diepoxybutane   Anticancer drugs (cyclophosphamide, chlorambucil, nitrosoureas, and others) (Many cancers especially leukemias) Acylating Agents1-Acetyl-imidazole  Dimethylcarbamyl chloride

52

What are some polycyclic and heterocyclic aromatic hydrocarbon procarcinogens that require metabolic activation?

Polycyclic and Heterocyclic Aromatic Hydrocarbons   Benz[a]anthracene  Benzo[a]pyrene  Dibenz[a,h]anthracene  3-Methylcholanthrene  7,12-Dimethylbenz[a]anthracene

53

What are some aromatic amines, amides, and azo -dyes that are procarcinogenic?

Aromatic Amines, Amides, Azo Dyes  2-Naphthylamine (β-naphthylamine)  Benzidine  2-Acetylaminofluorene  Dimethylaminoazobenzene (butter yellow)

54

What are some procarcinogenic plant and microbial products?

Natural Plant and Microbial Products  Aflatoxin B1  (Liver cancer via p53 inactivation)  Griseofulvin  Cycasin  Safrole  Betel nuts (Oral cancer)Others  Nitrosamine and amides  Vinyl chloride, nickel, chromium  Insecticides, fungicides  Polychlorinated biphenyls

55

Arsenic typically causes what kinds of occupation cancers? How is exposure mediated?

Lung carcinoma, skin carcinoma By-product of metal smelting; component of alloys, electrical and semiconductor devices, medications and herbicides, fungicides, and animal dips

56

Asbestos typically causes what kinds of occupation cancers? How is exposure mediated?

Lung, esophageal, gastric, and colon carcinoma; mesothelioma Formerly used for many applications because of fire, heat, and friction resistance; still found in existing construction as well as fire-resistant textiles, friction materials (i.e., brake linings), underlayment and roofing papers, and floor tiles

57

Benzene typically causes what kinds of occupation cancers? How is exposure mediated?

Acute myeloid leukemia Principal component of light oil; despite known risk, many applications exist in printing and lithography, paint, rubber, dry cleaning, adhesives and coatings, and detergents; formerly widely used as solvent and fumigant

58

Beryllium and beryllium compounds typically cause what kinds of occupation cancers? How is exposure mediated?

Lung carcinoma Missile fuel and space vehicles; hardener for lightweight metal alloys, particularly in aerospace applications and nuclear reactors

59

Cadmium and cadmium compounds typically cause what kinds of occupational cancers? How is exposure mediated?

Prostate carcinoma Uses include yellow pigments and phosphors; found in solders; used in batteries and as alloy and in metal platings and coatings

60

Chromium compounds typically causes what kinds of occupational cancers? How is exposure mediated?

Lung carcinoma Component of metal alloys, paints, pigments, and preservatives

61

Nickel compounds typically cause what kinds of occupational cancers? How is exposure mediated?

Lung and oropharyngeal carcinoma Nickel plating; component of ferrous alloys, ceramics, and batteries; by-product of stainless-steel arc welding

62

Radon and its decay products typically cause what kinds of occupational cancers? How is exposure mediated?

Lung carcinoma From decay of minerals containing uranium; potentially serious hazard in quarries and underground mines

63

Vinyl chloride typically cause what kinds of occupational cancers? How is exposure mediated?

Hepatic angiosarcoma Refrigerant; monomer for vinyl polymers (PVC industry); adhesive for plastics; formerly inert aerosol propellant in pressurized containers

64

Ultraviolet radiation causes what kinds of skin cancers?

•Nonmelanoma skin cancers - total cumulative exposure to UVB/UBC radiation•squamous cell carcinoma, basal cell carcinoma•Melanomas - intense intermittent exposure (sunbathing) 

65

Ionizing radiation - electromagnetic or particulate - can cause what kinds of tumors via what mechanisms?

•Medical or occupational exposure, nuclear plant accidents (decreasing order)•Acute and chronic myeloid leukemia•Cancer of the thyroid in the young•Cancers of the breast, lungs, and salivary glands•Radioactive mine workers have 10X increase in lung cancer•Cancers of skin, bone, and GI tract (x-ray researchers - skin cancers)•Atomic bomb detonations•Leukemias-principally acute and chronic myelogenous after 7 years•Solid tumors afterwards (e.g., breast, colon, thyroid, and lung) Intrinsic Field Subtractor - inability to wear clothing, blue skin coloration, exiling yourself to Mars, not killing Veidt and foiling his dastardly plan 

66

What RNA viruses are oncogenic? What cancers can they cause?

•HTLV-1 – adult T-cell leukemia/lymphoma•HCV – hepatocellular carcinoma 

67

What DNA viruses are oncogenic? What cancers can they cause?

•HBV – hepatocellular carcinoma•HPV- papillomas (types 1, 2, 4, 6, 7, & 11), carcinomas of cervix, anus, penis & oropharynx (types 16 &18)•HHV-8 – Kaposi sarcoma & primary effusion lymphoma•EBV – Burkitt lymphoma, Hodgkin lymphoma & nasopharyngeal carcinoma•CMV (HHV-5) – mucoepidermoid carcinoma•Merkel cell polyomavirus – Merkel cell carcinoma 

68

What fungi and parasite infections can cause cancer?

•Fungi•Aspergillus – aflotoxin B1-associated hepatocellular carcinoma (p53 mutation)•Parasites•Schistosoma haematobium – bladder cancer•Schistosoma japonicum – colon cancer•Opisthorchis viverrini – cholangiocarcinoma 

69

What bacterial infections can cause cancer?

•Helicobacter pylori – extranodal marginal zone (MALT) lymphoma and gastric adenocarcinoma 

70

What are 5 inherited autosomal recessive syndromes of defective DNA repair?

Xeroderma pigmentosum (nucleotide excision repair of cross-linked pyrimidine dimers)Hereditary nonpolyposis colon cancer syndrome  (DNA mismatch repair)Ataxia-telangiectasia (DNA repair by homologous recombination)Bloom syndrome (DNA repair by homologous recombination)Fanconi anemia (DNA repair by homologous recombination)

71

What are some examples where there are familial clustering of cancer cases, but the role of the inherited predisposition is unclear on an individual level?

Breast cancer (BRCA1 & BRCA2)Ovarian cancer (BRCA1 & BRCA2)Pancreatic cancer (BRCA2)

72

What are some inherited autosomal recessive conditions with defects in DNA repair?

Xeroderma pigmentosaAtaxia telangiectasiaBloom SyndromeFanconi anemia

73

What is abnormal in xeroderma pigmentosa, and what does it result in?

Autosomal recessive•Xeroderma pigmentosa - Nucleotide excision repair abnormality associated with extreme sensitivity to ultraviolet (UV) rays affects the eyes and skin (cancers), may also have CNS problems (increased pyrimidine dimers) 

74

What is abnormal in ataxia telangiectasia, and what does it result in?

Autosomal recessive•Ataxia telangiectasia – ATM gene defect (involved in DNA repair) associated with progressive difficulty with coordinating movements, weakened immune system, leukemias and lymphomas 

75

What is abnormal in Bloom syndrome, and what does it result in?

Autosomal recessive•Bloom syndrome – Helicase abnormality associated with short stature, sun-sensitive skin changes, an increased risk of cancer, and other health problems 

76

What is abnormal in Fanconi anemia? What does it result in?

Autosomal recessive•Fanconi anemia –  FA process defects associated with aplastic anemia, hypopigmentation, café-au-lait spots, skeletal problems, defects of the genitourinary tract; gastrointestinal tract; heart; eye and ears with hearing loss and acute myeloid leukemia 

77

What is abnormal in hereditary nonpolyposis colorectal cancer/Lynch syndrome? What does it result in?

Autosomal Dominant!•Hereditary nonpolyposis colorectal cancer (HNPCC) = Lynch syndrome  DNA mismatch repair abnormality leading to microsatellite instability associated with colorectal, endometrial, gastric, ovarian, ureteral, CNS, small bowel, hepatobiliary tract and skin cancers 

78

Match the following genes to the inherited predisposition:RBp53p16/INK4A

RB Retinoblastomap53 Li-Fraumeni syndrome (various tumors)p16/INK4A Melanoma

79

Match the following genes to the inherited predisposition:APCNF1, NF2BRCA1, BRCA2

APCFamilial adenomatous polyposis/colon cancer NF1, NF2Neurofibromatosis 1 and 2 BRCA1, BRCA2Breast and ovarian tumors

80

Match the following genes to the inherited predisposition:MEN1, RETMSH2, MLH1, MSH6PTCH

MEN1, RETMultiple endocrine neoplasia 1 and 2 MSH2, MLH1, MSH6Hereditary nonpolyposis colon cancer PTCHNevoid basal cell carcinoma syndrome

81

Match the following genes to the inherited predisposition:PTENLKB1=STK11VHL

PTENCowden syndrome (epithelial cancers)  LKB1=STK11Peutz-Jegher syndrome (epithelial cancers) VHLRenal cell carcinomas