Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas

This study reports the first use of gene array technology for the identific ation of a tumor-specific marker in lymphoid neoplasms. The differential ge ne expression of 31 hematopoietic cell lines, representing most major lymph oma subgroups of B- and T-cell origin, was assessed by hybridizing labeled complementary DNA to Atlas human expression arrays containing 588 genes. Ge nes known to be specific for B, T, or myelomonocytic lineages were appropri ately identified in the arrays, validating the general utility of this appr oach. One gene, clusterin, not previously known to be expressed in lymphoid neoplasms, was specifically found in all 4 anaplastic large-cell lymphoma (ALCL) cell lines, but not in any of the 27 remaining tumor lines. Using a monoclonal antibody against clusterin, its differential expression was conf irmed by Western blotting and immunohistochemistry. A total of 198 primary lymphomas (representing most major lymphoma subtypes), including 36 cases o f systemic ALCL, were surveyed for clusterin expression by immunohistochemi stry and Western blotting. All of the 36 ALCL cases marked for clusterin, w ith most cases showing moderate to strong staining in the majority of neopl astic cells. Clusterin expression was not related to expression of anaplast ic lymphoma kinase-1. With 2 exceptions, none of the remaining 162 non-ALCL cases marked with the clusterin antibody, including Hodgkin disease and pr imary cutaneous ALCL. In reactive lymphoid tissues, only follicular dendrit ic cells and fibroblastic reticular cells exhibited staining. Clusterin is a highly conserved glycoprotein implicated in intercellular and cell matrix interactions, regulation of the complement system, lipid transport, stress responses, and apoptosis, Although its function in ALCL is unknown, the un ique expression of clusterin within this category of lymphoma provides an a dditional marker for the diagnosis of ALCL, This study illustrates the enor mous potential of gene array technologies for diagnostic marker discovery. (C) 2000 by The American Society of Hematology.