Ch 7 - Neoplasia

Question 1

Normal cellular genes whose products promote cell proliferation

Answer 1

Proto-oncogenes

Question 2

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

Answer 2

Oncogenes

Question 3

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

Answer 3

Oncoprotein

Question 4

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

Answer 4

JAK2

Question 5

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

Answer 5

HER2

Gene is ERBB2

Question 6

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

Answer 6

RAS

Question 7

Transcription factor that is most commonly affected in cancer

Answer 7

MYC

Question 8

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

Answer 8

D cyclin genes and CDK4

Question 9

Action of RB on E2F transcription factors when hypophosphorylated?

Answer 9

Inhibition of E2 transcription factors

Question 10

How is RB inactivated by growth factors?

Answer 10

Hyperphosphorylation

Question 11

Syndrome where individuals have inherited mutations in TP53

Answer 11

Li-Fraumeni syndrome

Question 12

Inhibits p53 in normal healthy cells

Answer 12

MDM2

Question 13

Protein of HPV that can inactivate RB and p53

Answer 13

E6

Question 14

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

Answer 14

APC

Question 15

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

Answer 15

Beta-catenin

Question 16

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

Answer 16

CDKN2A

Question 17

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

Answer 17

VHL (von Hippel-Lindau)

Question 18

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.

Answer 18

PTEN

Question 19

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

Answer 19

Warburg effect

Question 20

Oncometabolite resulting from IDH mutations

Answer 20

2-hydroxyglutarate

Question 21

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

Answer 21

tumour dormancy

Question 22

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

Answer 22

p53

Question 23

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

Answer 23

xeroderma pigmentosum

Question 24

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

Answer 24

HNPCC (Lynch syndrome)

Question 25

Inflammatory mediators thought to play a role in cancer cachexia

Answer 25

TNF, IL-1, IL-6

Question 26

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

Answer 26

Paraneoplastic syndromes

Question 27

Tumours that are most often associated with paraneoplastic hypercalcaemia

Answer 27

Carcinomas of the breast, lung, kidney, ovary

Question 28

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

Answer 28

Anoikis

Question 29

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

Answer 29

Translocation

Question 30

The most common translocation seen in Burkitt lymphoma?

Answer 30

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

Question 31

Chromosomal change seen in acute promyelocytic leukaemia (APML)

Answer 31

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

Question 32

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

Answer 32

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

Question 33

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

Answer 33

Retinoblastoma

Question 34

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

Answer 34

Chromothrypsis | chromosome is "shattered" and then reassembled in a haphazard way

Question 35

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

Answer 35

NOTCH1

Question 36

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

Answer 36

- 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

Question 37

How are most indirect carcinogens metabolised?

Answer 37

By cytochrome p450 dependent monooxygenases

Question 38

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

Answer 38

CYP1A1

Question 39

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

Answer 39

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

Question 40

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

Answer 40

- 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.

Question 41

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

Answer 41

UVB (280-320nm)

Question 42

Mechanism by which UV radiation damages DNA

Answer 42

Causes pyrimidine dimers to form in DNA

Question 43

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

Answer 43

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

Question 44

Genes responsible for the oncogenic properties of HPV and their function

Answer 44

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

Question 45

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

Answer 45

70-85%

Question 46

Cancers associated with H.pylori infection

Answer 46

- gastric adenocarcinoma | - B cell lymphoma (MALToma)

Question 47

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

Answer 47

ERBB1

Question 48

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

Answer 48

BCL2 (an anti-apoptotic gene)

Question 49

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

Answer 49

Intrinsic (mitochondrial) pathway

Question 50

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

Answer 50

HIF1-alpha

Question 51

Growth factors transcribed by HIF1-alpha

Answer 51

VEGF | bFGF (basic fibroblast growth factor)

Question 52

Anti-angiogenic molecule stimulates by p53

Answer 52

Thrombospondin-1

Question 53

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

Answer 53

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)

Question 54

What is a carcinoma in situ?

Answer 54

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

Question 55

How to carcinomas tend to spread?

Answer 55

Via the lymphatics

Question 56

How do sarcomas tend to spread?

Answer 56

Haematogenous

Question 57

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

Answer 57

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

Question 58

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

Answer 58

tax and HBZ

Question 59

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

Answer 59

3-5%

Question 60

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

Answer 60

HTLV-1

Question 61

Which cells do HTLV-1 have tropism for?

Answer 61

CD4+ T cells

Question 62

Oncogene of EBV

Answer 62

Latent membrane protein 1 (LMP-1)

Question 63

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

Answer 63

LMP-1

Question 64

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

Answer 64

EBNA2

Question 65

Role of EBV in Burkitt lymphoma

Answer 65

- 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

Question 66

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

Answer 66

CagA