Application of Molecular Pathology

• How do cancers develop?

  • they have a Multi-hit pathogenesis
  • they need 2-6 genetic/epigenetic events
• What are mutation signatures? 2 important examples found in which cancers?

  • Signature 7 in skin cancers and in cancers of the lip
  • Signature 4 in head and neck cancer, lung adenocarcinoma, liver cancer and is associated with smoking
• What common mutations in cancers have been discovered by molecular techniques? - 5

  • BCL2 activation in follicular lymphoma caused by t(14;18)
  • BCR-ABL fusion protein on Philadelphia chromosome in chronic myeloid leukaemia t(9;22)
  • c-kit mutation in gastrointestinal stromal tumour
  • Activation of MYC oncogene in Burkitt lymphoma by t(8;14)
  • Translocations in sarcomas e.g. t(X;18) in synovial sarcoma
• How does FISH work → Fluorescent in situ hybridisation

  • in FISH, we detect the break of the gene SYT using SYT Dual Color, Break Apart Rearrangement Probe. In a positive sample for rearrangement of the gene SYT, we observe one yellow, one red, and one green signal. In negative samples, we observe two yellow signals.