Determination of Cyclin D1 Expression by Quantitative Real-Time, Reverse-Transcriptase Polymerase Chain Reaction
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Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. The gene encoding the cyclin D1 protein, a regulator of the progression from the G1- to S-phase, is often found disrupted in the cancer cell genome by the processes of chromosome translocation or gene amplification. Regardless of the mechanism, the end result of these genetic alterations is overexpression of the cyclin D1 mRNA and the protein it encodes. Among the tumors in which cyclin D1 overexpression has been observed are carcinomas of the breast (1 ,2 ), colon (3 ), larynx and esophagus (4 ,5 ), lung (6 ), bladder (7 ), and ovary (8 ,9 ), multiple myeloma (10 ), and parathyroid adenoma (11 ). However, the detection of overexpression or the specific chromosome translocation responsible for it has found clinical utility primarily in the diagnosis of mantle cell lymphoma, a small lymphocytic lymphoma composed of CD5-positive, CD10-negative B-lymphocytes that can be mistaken histologically for other types of B-cell non-Hodgkin’s lymphoma (12 –14 ). The distinction is important because mantle cell lymphomas have a less favorable prognosis and require more aggressive therapy than other, microscopically similar lymphomas (15 ). Genetically, nearly all mantle cell lymphomas have a characteristic translocation, t(11;14) (q13;q32). The translocation breakpoints on chromosome 11q13 invariably lie near the Cyclin D1 gene at that locus, with about one-third lying within the short segment of DNA designated as the major cluster region.