7. mechanism of neoplasia in practise

Question 1

what do growth mechanisms do and how can they be mediated?

Answer 1

ensure that rate of cell division= apoptosis

an imbalance causes tumour

• Levels of secreted growth factors
• Environmental growth inhibitory factors
• Levels of secreted growth inhibitors
• Intrinsic program of differentiation/apoptosis
• Tumour immune response

Question 2

self sufficiency of growth signals

Answer 2

1. Increased secretion of growth factors.
   * Insulin like growth factor 2 (IGF2) upregulated in Wilm’s tumour.
2. Upregulation of growth factor receptor
   * cErbB2 (member of the EGFR family) upregulated in breast cancer
3. Activation of growth factor receptors
   * Mutation in the TK domain of c-Kit (receptor for Stem Cell Factor) in GISTS (gastro-intestinal stromal tumours)

Question 3

Evasion of apoptosis

Answer 3

Evasion of apoptosis may occur through:

• Upregulation of anti-apoptotic factors
• Bcl2 is upregulated in follicular lymphomas due to the 1(14;18) chromosome translocation – gene is put in front of another promotor is switched on due to transcription of that translocation

Down-regulation of pro-apoptotic factors

• Caspase 3 is down-regulated in colorectal tumours
• Loss of function of pro-apoptotic factors
• Tp53 is mutated in colorectal tumours

Question 4

Refining diagnosis

Answer 4

Knowledge of the genetic changes in a tumour may refine diagnosis by:

(a) Identifying mutations characteristic of a tumour type. These mutations can then be used as a diagnostic test
* c-Kit mutations in gastro-intestinal stromal tumours (GIST); t(X;18) in synovial scarcomas; t(2;13) in alveolar rhabdomyosarcoma; t(9;22) in Chronic Myeloid Leukaemia
(b) Identifying genetic subgroups within a morphologically uniform group of tumours
* Diffuse large B cell lymphomas are a homogeneous group histologically but can be shown, on expression profiling, to be two different groups with different prognoses- use characteristics of breast tumours to stain tumour and see if match
(c) Identifying new prognostic factors
* Loss of 18q is a poor prognostic marker in early stage colorectal cancers; the level of n-myc amplification is important in neuroblastoma.

Question 5

Hallmarks of cancer

Answer 5