Cytogenetics — Chromosome Analysis in Cancer

Cytogenetics involves the microscopic and molecular analysis of chromosomes extracted from dividing cells. In malignant tissues, acquired genomic alterations often disrupt normal cellular growth pathways. By evaluating the karyotype—the complete set of paired chromosomes—pathologists and geneticists can detect large-scale structural disruptions and numerical abnormalities (aneuploidy) that characterise particular cancers.

Modern diagnostic cytogenetics relies on several complementary techniques, including conventional G-banded karyotyping, fluorescence in situ hybridisation (FISH), and comparative genomic hybridisation (CGH). These tests allow clinicians to pinpoint specific genetic rearrangements, establishing precise sub-classifications of disease that directly guide risk assessment and targeted treatment options.

Cytogenetic findings are vital for modern precision oncology. They often reveal whether a malignancy is fast-growing or indolent, which helps doctors assign patients to standard-risk or high-risk treatment pathways. Furthermore, identifying specific chromosomal rearrangements allows oncologists to prescribe therapies designed to counteract those exact genetic faults, sparing patients from ineffective treatments and helping clinicians track residual disease over time.

Cytogenetic testing is performed on fresh tissue, bone marrow aspirates, or blood samples containing dividing cells. Conventional karyotyping visualises intact metaphase chromosomes under light microscopy. Fluorescence in situ hybridisation (FISH) uses fluorescent probes that bind to specific DNA sequences to identify translocations, such as the *BCR-ABL1* fusion, or gene amplifications like *ERBB2* (HER2), even in non-dividing cells.

Cytogenetics plays an indispensable role in haematological malignancies, including acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL), myelodysplastic syndromes, and multiple myeloma. It is also increasingly applied to solid tumours such as soft tissue sarcomas (including Ewing sarcoma and synovial sarcoma), neuroblastoma, and certain central nervous system tumours.

Chromosomal findings directly influence drug selection. The landmark example is the Philadelphia chromosome [t(9;22)], which creates the *BCR-ABL1* fusion gene in CML, treated with tyrosine kinase inhibitors such as imatinib. In acute promyelocytic leukaemia, the t(15;17) translocation responds to targeted all-trans retinoic acid (ATRA) and arsenic trioxide. Cytogenetic risk also dictates whether a patient needs an allogeneic stem cell transplant.