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TCM (microbio) > Neoplasia > Flashcards

Neoplasia Flashcards

1
Q

What is a major cause of polycythemia assuming a paraneoplastic syndrome?

A

Renal carcinoma (gastric) that cause excessive secretion of erythropoietin.

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2
Q

PAX 5 gene mutation can lead to what?

A

B-cel leukemia/lymphoma

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3
Q

Dermatomyositis???

A

Connective tissue disorder of the muscle and connective tissue. Commonly seen with Gottron’s sign (red, scaly papules on finger).

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4
Q

C-MYC

A

Translocation of this transcription factor will lead to Burkitt Lymphoma.

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5
Q

Tumor Marker alpha-fetoprotein

A

Liver cell cancer, nonseminomatous germ cell tumor of testis.

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6
Q

What is carcinoid syndrome?

A

Paraneoplastic syndrome characterized by elevated secretion of Bradykinin and Serotonin that leads to: flushing and diarrhea, and less frequently, heart failure, emesis and bronchoconstriction.

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7
Q

Role of Rb?

A

Tumor suppressor that binds E2F factors, preventing G1/S progression. Interacts with other transcription factors that regulate differentiation.

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8
Q

PAX 3/ PAX 7 gene mutations can lead to what?

A

Embryonal rhabdomyosarcoma.

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9
Q

Cowden syndrome is the result of what abnormality?

A
  1. Mutation to the PTEN gene affects phosphatase and tensin homologues in the PI3K/AKT signaling pathway.
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10
Q

Tumor Marker CA-15-3

A

Breast cancer.

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11
Q

Li-Franumeni syndrome.

A

Caused by a mutation to TP53, leading to loss of tumor suppressor protein p53. Allows for unregulated cell growth/replication. Cause of DIVERSE amount of human cancers.

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12
Q

What is the major cause of syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

A

Small cell carcinoma of lung/intracranial neoplasms. Increases the anti-diuretic hormone.

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13
Q

Mutation to the VHL gene will lead to what diseases?

A
  1. Familial: Von Hippel Lindau syndrome (retinal angioma, cerebellar hemangioblastoma, islet cell tumors, pheochromocytoma, pancreatic cysts).
  2. Sporadic: Renal cell carcinoma.
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14
Q

What is the role of p53?

A

Tumor suppressor that is majorly altered in most cancers. Causes cell cycle arrest and apoptosis with normal function. indirect relationship with MDM2 for activation. Required for progression for G1/S checkpoint and G2/M checkpoint. High MDM2 reduces p53 leading to rapid cell growth. Low levels of MDM2 increase the p53, causing apoptosis/cell cycle arrest.

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15
Q

What causes nevoid basal cell carcinoma (Gorlin’s syndrome)?

A
  1. Mutation in the PTCH(1) gene affects the patched protein leading to altered function of the Hedgehog signaling pathway.
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16
Q

Bloom syndrome

A

Helicase abnormality in DNA repair, causes short stature, sun sensitive skin, and increased cancer risk . Autosomal recessive DNA repair defect.

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17
Q

BRCA1/BRCA2 gene mutations can lead to ?

A

Familiar breast and ovarian carcinoma. Rarely have a sporadic form that develop.

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18
Q

Walk through the steps of the metastatic cascade.

A
  1. Loss of desmosomes, allow movement by removal of tumor cell and cell interactions.
  2. Degradation of ECM via collagenase.
  3. Attachment to the new ECM components.
  4. Migration of tumor cell into the vessel/ or along the vessel.
  5. Clumping of tumor cells within the vessel.
  6. Adhesion of tumor cells to the endothelium.
  7. Egression of tumor cells through the vascular basement membrane.
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19
Q

Von hippel Lindau syndrome can be attributed to what?

A
  1. A mutation of the VHL gene within the VHL protein that inhibits the hypoxia induced transcription factor. Constitutive activation of HIF-1 promotes angiogenesis.
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20
Q

What is a thymoma?

A

Neoplasm, responsible for production of Ab against ACHR that can lead to myasthenia gravis. Would be considered a paraneoplastic syndrome.

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21
Q

The sporadic form of renal cell carcinoma can most likely be traced back to what?

A
  1. A mutation of the VHL gene within the VHL protein that inhibits the hypoxia induced transcription factor. Constitutive activation of HIF-1 promotes angiogenesis.
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22
Q

RB(1) gene mutation leads to what familial/sporadic diseases?

A
  1. Familial: familial retinoblastoma.

2. Sporadic: osteosarcoma.

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23
Q

L-MYC

A

Amplification of this will lead to small cell carcinoma of the lung.

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24
Q

What is the most likely culprit of lung cancer with hypercalcemia?

A
  1. Squamous cell carcinoma that has NOT metastasized to the bone.
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25
Q

A mutation of NF2 gene can lead to what?

A
  1. Familial neurofibromatosis type II (acoustic neuroma)

2. Sporadic schwannoma, meningioma

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26
Q

Arsenic causes

A

skin carcinoma

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27
Q

How are tumor cells able to evade the immune system?

A
  1. Tumor fails to produce an antigen.
  2. Cause mutation in the MHC or MHC genes that are required to process the antigen signal.
  3. Produce immunosuppressive proteins or inhibitory surface proteins.
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28
Q

Tumor Marker prostatic acid phosphatase

A

Prostate cancer

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29
Q

Fanconi anemia

A

Autosomal recessive DNA defect repair. Seen with aplastic anemia, hypopigmentation, café-au-lait spots, hearing loss, acute myeloid leukemia.

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30
Q

Grading cancer

A

Degree of differentiation of the tumor cells.

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31
Q

ALK

A

Translocation of ALK receptor leads to adenocarcinoma of the lungs. A point mutation can lead to a neuroblastoma.

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32
Q

Dermatomyositis. Suspect what type of cancer?

A

Bronchogenic, breast carcinoma.

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33
Q

Translocation of (11:22) will lead to what malignancy?

A

Ewing sarcoma. FLI 11: EWSR22.

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34
Q

Xeroderma pigmentosa

A

Autosomal recessive defective DNA repair mutation. Lack of Nucleotide excision repair. No removal of pyrimidine dimers.

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35
Q

N-MYC

A

Amplification of this will lead to neuroblastoma

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36
Q

Radon causes…

A

Lun carcinoma.

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37
Q

Oncogenic parasites

A
  1. Schistosoma haematobium- bladder cancer.
  2. s. japonicum- colon cancer.
  3. Opisthorchis viverrini- cholagniocarcinoma.
38
Q

PTEN gene mutation will lead to what Familial/Sporadic disease?

A
  1. Familial: Cowden syndrome (skin, thyroid mostly)

2. Sporadic: diverse set of cancers.

39
Q

Tumor Marker carcinoembryonic antigen.

A

Carcinoma of colon, pancreas, lung, stomach, heart.

40
Q

Ataxia-telangiectasia

A

ATM gene defect involved in DNA repair by homologous recombination. Increased difficulty in coordinating movements. Autosomal recessive defective DNA repair.

41
Q

What is the major cause of hypercalcemia assuming a paraneoplastic syndrome?

A

Squamous cell carcinoma of the lung. This increases the parathyroid hormone related protein, TGF, TNF, IL-1.

42
Q

Staging cancer

A

Provides prognostic based on the size of primary lesions, extent of spread to regional LN, and +/- of blood borne metastasis (T;N:M) respectively.

43
Q

Neurofibromatosis type II.

A

Familial syndrome due to mutation of NF2 gene affecting merlin protein. Leads to meningioma and ependymoma.

44
Q

A mutation to NF1 gene can lead to what?

A
  1. Familial neurofibromatosis type I.

2. Sporadic neuroblastoma, juvenile myeloid leukemia.

45
Q

What is responsible for the symptoms that are seen in a paraneoplastic syndrome?

A
  1. Products produced by the tumor cells (hormones)

2. Immune reaction of the body to the product of the tumor cells (myasthenia gravis)

46
Q

What is the major cause of carcinoid syndrome as a paraneoplastic syndrome?

A

Hepatocellular carcinoma, bronchial adenoma, and pancreatic carcinoma. Can lead to increased levels of serotonin, and bradykinin. these will lead to: flushing and diarrhea, and less frequently, heart failure, emesis and bronchoconstriction.

47
Q

Translocation of (8:14) will cause what malignancy?

A

Burkitt Lymphoma. c-MYC8/ IGH14

48
Q

Hereditary nonpolyposis colorectal cancer (HNPCC) [Lynch Syndrome]

A

DNA mismatch repair abnormality leading to micro satellite instability. Common with colorectal cancer, endometrial, gastric, ureteral, small bowel, hepatobiliary tract and skin cancer.

49
Q

Tumor Marker immunoglobulins.

A

multiple myeloma and other gammopathies.

50
Q

What is the Warburg effect?

A
  1. Cancer cells shift their metabolism to AEROBIC glycolysis. This provides the amount of energy required along with the intermediate proteins/components that can be used to rapidly increase the number of cells. 95% of glucose is used to produce metabolic intermediates used in synthesis of cellular components and 4mol ATP/ 1 glucose. (instead of normal like 36mol/1 glucose).
51
Q

Tumor Marker calcitonin

A

Medullary carcinoma of thyroid.

52
Q

What is the normal function of p53 gene?

A

Produce p53, and cause cell cycle arrest and apoptosis based on DNA damage.

53
Q

Oncogenic fungi:

A

Aspergillus-aflatoxin B1

54
Q

Tumor Marker neuron-specific enolase

A

small cell cancer of lung, neuroblastoma

55
Q

Translocation of (9:22) will cause what malignancy?

A

Chronic myelogenous leukemia. ABL 9q34 translocation BCR

56
Q

Myasthenia gravis as a paraneoplastic syndrome, should suspect what type of cancer?

A

thymic neoplasm.

57
Q

Acanthosis nigricans. Suspect what type of cancer?

A

Gastric, lung, uterine carcinomas. Immunological secretion of epidermal growth factor.

58
Q

Vinyl chloride…

A

The monomer precursor before forming PVC pipe. The vinyl chloride monomer can induce hepatic angiosarcoma (hepatoma)

59
Q

What unequivocally marks a tumor as being malignant?

A

Metastasis. Benign tumors have the ability to “spread” but should not metastasize.

60
Q

What is the rate of tumor growth dependent on?

A
  1. Doubling time (less time to double=more aggressive).
  2. Fraction of cells in replicative pool.
  3. Rate at which cells are shed/die.
    * *blood supply, hormonal factors, emergence of aggressive sub-clones.**
61
Q

What is the normal function of CDK4/cyclin-D?

A

This complex works to Hyperphosphorylate Rb. This inactivates the protein allowing cell cycle progression through G1/S. Hypophosphorylation will prevent cell cycle progression.

62
Q

Asbestos causes…

A

Lung, esophageal, gastric, colon carcinoma and mesothelioma.

63
Q

Break down of “E-cadherin” promotes what activity?

A
  1. E-cadherin breakdown promotes cell motility and can allow for gastric and lobular breast carcinoma development.
64
Q

KRAS

A

Point mutation of this GTP-binding protein leads to colon, lung, pancreatic tumors.

65
Q

GNAS

A

Point mutation of this GTP-binging protein leads to pituitary adenoma.

66
Q

Ancanthosis nigricans

A

Brown to black hyperpigmented region of skin that should not be “tanning”

67
Q

Small cell carcinoma of the lung.

A

Neuroendocrine due to mutation of cells that produce endocrine molecules and neuropeptides.

68
Q

NRAS

A

Point mutation of this GTP-binding protein leads to melanomas, hematologic malignancies.

69
Q

What is the role of INK4/ ARF family?

A

INK4 binds cyclin-D-CDK4 complex to promote the inhibitory effect of RB (no cell cycle progression). While ARF increases p53 levels by blocking MDM2.

70
Q

What are the common neoplasms of infancy and childhood?

A
  • *small round blue cell tumors**
    1. Neuroblastoma.
    2. Wilm’s Tumor.
    3. Retinoblastoma.
    4. Acute leukemia/lymphomas.
71
Q

Oncogenic DNA virus:

A
  1. HBV: heptaocellular carcinoma.
  2. HPV: cervix, anal genital warts, papilloma.
  3. HHV-8: kaposi sarcoma related. Primary effusion lymphoma.
  4. EBV: burkitt, hodgkin nasopharyngeal carcinoma.
72
Q

Neurofibromatosis-1

A

Familial syndrome of neurofibromas and malignant peripheral nerve sheath tumors. Caused by mutation of NF1 gene.

73
Q

Tumor Marker human chorionic gonadotropin (hCG)

A

trophoblastic tumor, nonseminomatous testicular tumor

74
Q

Cancer Cachexia.

A

Progressive loss of body fat and lean body mass in equal proportions. Associate with profound weakness, anorexia, and anemia. Can mimic Marasmus-like protein-energy malnutrition by high levels of TNF-alpha.

75
Q

Tumor Marker prostate-specific antigen (PSA)

A

prostate cancer. But very low specificity and low sensitivity.

76
Q

Tumor Marker ectopic hormones.

A

Paraneoplastic syndromes.

77
Q

PAX8 gene mutation can lead to what?

A

Renal, thyroid, and ovarian carcinomas.

78
Q

Oncogenic bacteria:

A

H. pylori- extranodal marginal zone MALT lymphoma and gastric adenocarcinoma.

79
Q

What is the major cause of Cushing’s Syndrome?

A

Small cell carcinoma of the lung that leads to increased secretion of ACTH or ACTH-like substances.

80
Q

Tumor Marker CA-125.

A

Ovarian cancer

81
Q

RET

A

Receptor for neurotrophic factors. A point mutation leads to Multiple endocrine neoplasia 2A/2B.

82
Q

PTCH(1) gene mutation leads to what familial/sporadic diseases?

A
  1. Familial: Nevoid basal cell carcinoma (Gorlin Syndrome)

2. Sporadic: Basal cell carcinoma.

83
Q

What is a broad definition of the “paraneoplastic syndromes”?

A

is a syndrome (a set of signs and symptoms) that is the consequence of cancer in the body but that, unlike mass effect, is not due to the local presence of cancer cells.[1] In contrast, these phenomena are mediated by humoral factors (such as hormones or cytokines) excreted by tumor cells or by an immune response against the tumor.

84
Q

ABL (Philadelphia chromosome)

A

Translocation of this nonreceptor tyrosine kinase proto-oncogene leads to chronic myeloid leukemia. A point mutation will lead to acute lymphoblastic leukemia.

85
Q

Bezene causes…

A

Acute myeloid leukemia.

86
Q

Tumor Marker CA-19-9

A

Colon, pancreatic cancer.

87
Q

Oncongenic RNA viruses

A
  1. HTLV-2: human T-cell leukemia.

2. HCV: hepatocellular carcinoma.

88
Q

ERBB2 (HER)

A

Activated by amplification. Leads to breast carcinoma.

89
Q

KIT

A

Point mutation in receptor for KIT ligand. Leads to Gastrointestinal stromal tumors. (seminomas, and certain leukemias)

90
Q

What are the “patterns of metastasis”?

A
  1. Direct seeding: moving tissue into other regions. Or cancer breaks through a surface and invades to grow in a cavity.
  2. Hematogenous Spread: normally seen with sarcoma, and use of venous invasion via the tumor cells.
  3. Lymphatic spread: normally seen in carcinoma, use of “sentinel lymph node theory”.
91
Q

ERBB1 (EGFR)

A

Acitvated by mutation. Leads to lung adenocarcinoma.

92
Q

Tumor Marker catecholamine and metabolites

A

Pheochromocytoma and related.

TCM (microbio) (7 decks)

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