In various types of lung cancer, the following genes are damaged: EGFR, K-RAS, BRAF, ALK and many others, and the changes usually affect several genes simultaneously. Such disorders are detected at various levels of the structure of the genetic material: in the morphology of the chromosomes (karyotyping disorders), the number of gene copies (gene loss or duplication) or the gene structure (rearrangements, gene fusions), as well as in disorders of single DNA nucleotides (mutations). How is gene damage detected in varieties of lung cancer?
Gene damage in varieties of lung canceris detected by advances in genetics. Currently, it is possible to detect a huge number of different types of defined genetic disorders. In the cytogenetic and molecular diagnostics laboratories, tests are performed to detect and assess aberrations specific to the cells of the neoplastic tissue.
Lung cancer: the role of genetics
The test material is tumor cells collected during surgery (this is usually the case in lung cancer): in the case of leukemias, the neoplastic cells are in the cancerous bone or blood, and in the case of lymphomas, the lymph nodes are affected. A geneticist can assess changes in the number and structure of chromosomes or the status of specific genes or selected regions of DNA. Interpretation of these data, made on the basis of modern knowledge and applicable diagnostic principles, indicates the possible clinical effects of the aberration and is of key importance in the diagnosis of many types of neoplasms. - The results of genetic testing largely influence clinical decisions today - says prof. Barbara Pieńkowska-Grela, Specialist in Laboratory Medical Genetics (Cancer Genetics Laboratory, Department of Pathology at the Oncology Center).
Lung cancer: genetic research methods
The laboratories use various methods of staining chromosomes, which allow to see deviations from their normal morphology. Gene disorders (quantitative and qualitative) are detected in tests using the FISH technique. This technique uses "DNA probes" - that is, defined (known) stretches of DNA - labeled with a special dye. The probe specifically binds to the complementary DNA sequence of the patient's cancer cell, e.g. the ALK gene, and the associated dye allowsto see the studied area of DNA under a fluorescence microscope. ALK rearrangement, which occurs on chromosome 2, produces an EML4-ALK fusion and changes the properties of the protein product of the ALK gene. The use of several DNA probes simultaneously highlights the location and mutual relations of the studied genes. The FISH method can be used in the examination of archival material of the tumor (paraffin sections). The material for the analysis of genetic changes is initially assessed by a pathologist who selects the neoplastic lesion. Disorders of the studied genes in a neoplastic cell are of diagnostic importance in a specific clinical situation. A more detailed molecular examination allows to determine changes inside the studied genes, i.e. mutations, leading to specific disturbances in the functioning of an apparently normal gene.
Lung cancer: molecular targeted therapy
The future of cancer treatment is MOLECULARLY TARGETED THERAPY, ie the use of a drug directed against a cancer cell with a specific genetic change. Such drugs are highly effective, however, as long as there is a MOLECULAR TARGET in the tumor cell of the patient being treated. This target is a specific altered gene / protein resulting from the template of the abnormal gene. Even the best drug will not work unless we find a molecular target for it. For this reason, a necessary condition for the success of targeted therapy is a thorough genetic evaluation of tumor cells and the determination of the expected patient susceptibility to treatment.
press materials of the Polish Lung Cancer Group and the Oncology Center