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BPS Exam Study > Ch 7 - Neoplasia > Flashcards

Ch 7 - Neoplasia Flashcards

1
Q

Normal cellular genes whose products promote cell proliferation

A

Proto-oncogenes

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2
Q

Mutated or overexpressed versions of proto-oncogenes that function autonomously, having lost dependence on normal growth promoting signals

A

Oncogenes

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3
Q

A protein encoded by an oncogene that drives increased cancer cell proliferation, which may result from a variety of aberrations

A

Oncoprotein

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4
Q

Activation of this tyrosine kinase by point mutations is often involved in myeloproliferative neoplasms

A

JAK2

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5
Q

This tyrosine kinase receptor of the EGF-receptor family is often affected by gene amplification in breast cancer.

A

HER2

Gene is ERBB2

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6
Q

Point mutations of this family of genes constitute the most common abnormality involving proto-oncogenes in human tumours

A

RAS

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7
Q

Transcription factor that is most commonly affected in cancer

A

MYC

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8
Q

Gain of function mutations in these cyclin/CDK genes promotes unregulated G1S progression

A

D cyclin genes and CDK4

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9
Q

Action of RB on E2F transcription factors when hypophosphorylated?

A

Inhibition of E2 transcription factors

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10
Q

How is RB inactivated by growth factors?

A

Hyperphosphorylation

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11
Q

Syndrome where individuals have inherited mutations in TP53

A

Li-Fraumeni syndrome

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12
Q

Inhibits p53 in normal healthy cells

A

MDM2

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13
Q

Protein of HPV that can inactivate RB and p53

A

E6

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14
Q

Germline mutations affecting this tumour suppressor gene are associated with familial adenomatous polyposis

A

APC

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15
Q

The target of APC which translocates to the nucleus and binds to TCF as part of the WNT signaling pathway

A

Beta-catenin

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16
Q

This gene encodes two protein products:
- p16/INK4a cyclin-dependent kinase inhibitor
- p14/ARF which activates the p53 pathway
Germline mutations of this are associated with familial forms of melanoma and sporadic mutations have been implicated in other cancers

A

CDKN2A

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17
Q

Encodes a component of a ubiquitin ligase complex that is responsible for degradation of hypoxia-induced factors (HIFs), transcription factors that alter gene expression in response to hypoxia
Mutations associated with renal cell carcinoma

A

VHL (von Hippel-Lindau)

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18
Q

Encodes a lipid phosphatase that is an important negative regulator of Pi3K/AKT signaling.
Germline mutations cause Cowden syndrome, an autosomal dominant disorder associated with a high risk of breast and endometrial carcinoma.
Biallelic loss of function common in diverse cancers.

A

PTEN

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19
Q

Term for the distinctive form of cellular metabolism displayed by cancer cells characterised by high levels of glucose uptake and increased conversion of glucose to lactose via the glycolytic pathway

A

Warburg effect

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20
Q

Oncometabolite resulting from IDH mutations

A

2-hydroxyglutarate

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21
Q

phenomenon whereby metastatic cells take root and survive within different tissues but fail to grow

A

tumour dormancy

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22
Q

Loss of this protein function is the preeminent source of genomic instability in cancers

A

p53

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23
Q

Syndrome due to inherited loss of function in genes involves in nucleotide excision repair. Associated with high risk of skin cancers

A

xeroderma pigmentosum

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24
Q

Patients with this syndrome have defects in the mismatch repair system. Genome shows microsatellite instability, characterised by changes in the length of short repeats throughout the genome

A

HNPCC (Lynch syndrome)

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25
Q

Inflammatory mediators thought to play a role in cancer cachexia

A

TNF, IL-1, IL-6

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26
Q

signs and symptoms that cannot readily be explained by the anatomic distribution of the tumour or by the elaboration of hormones indigenous to the tissue from which the tumour arose

A

Paraneoplastic syndromes

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27
Q

Tumours that are most often associated with paraneoplastic hypercalcaemia

A

Carcinomas of the breast, lung, kidney, ovary

28
Q

programmed cell death occurring upon cell detachment from the correct extracellular matrix, thus disrupting integrin ligation

A

Anoikis

29
Q

What is the most common chromosomal rearrangement that activates proto-oncogenes?

A

Translocation

30
Q

The most common translocation seen in Burkitt lymphoma?

A

MYC containing segment of chromosome 8 moves to chromosome 14q32 placing it close to the immunoglobuin heavy chain gene

31
Q

Chromosomal change seen in acute promyelocytic leukaemia (APML)

A

Reciprocal translocation between chromosomes 15 and 17 producing a PML-RARA fusion gene

32
Q

all-trans retinoic acid binding to PML-RARa in cases of APML is the first example of what kind of treatment

A

differentiation therapy (immortal tumour cells are induced to differentiate into their mature progeny which have limited lifespans)

33
Q

Deletions involving chromosome 13q14 are associated with what type of cancer

A

Retinoblastoma

34
Q

Chromosome ‘shattering’ that occurs in about 1-2% of cancers; more common in osteosarcomas and gliomas.

A

Chromothrypsis

chromosome is “shattered” and then reassembled in a haphazard way

35
Q

This gene is a commonly mutated tumour suppressor gene in SCC and also the most commonly mutated oncogene in T-cell acute lymphoblastic leukaemia

A

NOTCH1

36
Q

What are the 2 categories of chemicals that can cause initiation of carcinogenesis and what is the difference between them?

A
  • Direct acting: do not require metabolic conversion to become carcinogenic
  • Indirect acting: require metabolic conversion to become active carcinogens; the carcinogenic products are called ultimate carcinogens
37
Q

How are most indirect carcinogens metabolised?

A

By cytochrome p450 dependent monooxygenases

38
Q

Gene involved in metabolising polycyclic aromatic hydrocarbons such as benzo[a]pyrene
Susceptible form significantly increases risk of lung cancer from smoking

A

CYP1A1

39
Q

There is a strong correlation between the dietary level of this food contaminant and the incidence of hepatocellular carcinoma in Africa and the Far East

A

Aspergillus (grows on improperly stored grains and nuts. Produces aflatoxin B1)

40
Q

Explain the difference between initiators and promoters in the initiation-promoter sequence of carcinogenesis

A
  • initiation results from exposure of cells to a sufficient dose of a carcinogenic agent that causes permanent DNA damage
  • promoters: can induce tumours to arise from initiated cells, but they are not tumourigenic themselves.
41
Q

Which form of UV radiation is the most significant in the formation of cancer and what is its wavelength?

A

UVB (280-320nm)

42
Q

Mechanism by which UV radiation damages DNA

A

Causes pyrimidine dimers to form in DNA

43
Q

Oncogenic RNA virus firmly implicated in the pathogenesis of cancer in humans

A

Human T-cell Leukaemia Virus Type 1 (HTLV-1)

44
Q

Genes responsible for the oncogenic properties of HPV and their function

A

E6 - degradation of p53 and increases expression of TERT
E7 - binds to Rb and displaces E2F transcription factors promoting progression through cell cycle
inactivates p21 and p27

45
Q

What proportion of hepatocellular carcinomas worldwide are associated with Hep B or Hep C infection?

A

70-85%

46
Q

Cancers associated with H.pylori infection

A
  • gastric adenocarcinoma

- B cell lymphoma (MALToma)

47
Q

Several different point mutations of this gene encoding EGFR are found in a subset of lung adenocarcinomas

A

ERBB1

48
Q

Which gene is overexpressed in over 85% of follicular B cell lymphomas?

A

BCL2 (an anti-apoptotic gene)

49
Q

Lesions that incapacitate which pathways of cell death are the most common in cancers?

A

Intrinsic (mitochondrial) pathway

50
Q

Relative lack of oxygen stabilises this transcription factor that activates pro-angiogenic factors

A

HIF1-alpha

51
Q

Growth factors transcribed by HIF1-alpha

A

VEGF

bFGF (basic fibroblast growth factor)

52
Q

Anti-angiogenic molecule stimulates by p53

A

Thrombospondin-1

53
Q

Are nuclei likely to be larger or smaller in malignant cells?

A

Characteristically, cancer cells have nuclei that are disproportionately large
(nuclear to cytoplasm ratio may approach 1:1 instead of the normal 1:4 -1:6)

54
Q

What is a carcinoma in situ?

A

When dysplasia is severe and involves the full thickness of the epithelium but the lesion does not penetrate the basement membrane

55
Q

How to carcinomas tend to spread?

A

Via the lymphatics

56
Q

How do sarcomas tend to spread?

A

Haematogenous

57
Q

What are the three mechanisms by which HIV is transmitted to the newborn child?

A
  1. In utero by transplacental spread
  2. During delivery through an infected birth canal
  3. After birth by ingestion of breast milk
58
Q

What 2 genes are thought to be involved in the pathogenesis of ATLL from HTLV-1

A

tax and HBZ

59
Q

What proportion of people infected with HTLV-1 develop leukaemia?

A

3-5%

60
Q

Which human retrovirus is firmly implicated in the pathogenesis of cancer in humans?

A

HTLV-1

61
Q

Which cells do HTLV-1 have tropism for?

A

CD4+ T cells

62
Q

Oncogene of EBV

A

Latent membrane protein 1 (LMP-1)

63
Q

EBV gene that activates NF-kB and JAK/STAT signaling pathways and promotes B cell survival and proliferation
Prevents apoptosis by activating BCL-2

A

LMP-1

64
Q

EBV protein that encodes a nuclear protein that mimics a constitutively active Notch receptor

A

EBNA2

65
Q

Role of EBV in Burkitt lymphoma

A
  • not directly oncogenic
  • acts as a polyclonal B cell mitogen which sets the stage of the acquisition of the (8;14) translocation and other mutations that ultimately produce cancer
66
Q

Gene of H. pylori that may contribute to carcinogenesis by stimulating growth factor pathways

A

CagA

BPS Exam Study (12 decks)

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