Cytogenetics, in situ hybridization and molecular approaches in the diagnosis of cancer

The past 100 years represent almost the entire history of the recognition of the role of genetics in human cancer. The purpose of this work is to: 1) review that history; 2) explore the techniques that have brought cancer genetics to its present state of knowledge; and 3) to provide preliminary data on how cytogenetics, fluorescence in situ-hybridization (FISH) and molecular techniques contribute to the diagnosis of chronic myelogenous leukemia (CML). Conventional cytogenetics provided the first chromosomal marker for malignancy in 1960. This was to be known as the so-called Philadelphia chromosome. Additional chromosomal changes associated with various hematologic malignancies followed in the 1970s after chromosomal banding was perfected. FISH, polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR) and other molecular techniques followed. Using these techniques, the diagnosis and prognosis of CML continue to evolve. The current study evaluates 21 patients by conventional cytogenetics and compares the percentage of t(9;22) metaphases with FISH information on the bone marrow and peripheral blood specimens of the same patients. The correlation of the techniques in this small study is 100 percent. Depending on the cutoff for abnormal FISH, 10 percent or less of the FISH studies on bone marrow or peripheral blood are false negatives. Conventional cytogenetics is used as the present gold standard. FISH and molecular techniques are complementary and will provide additional significant information in the future.