Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma
| Autor: | Hiro Nitta, Dennis D. Weisenburger, James R. Cook, Jan Delabie, Patrick Brunhoeber, Nathalie A. Johnson, Andreas Rosenwald, Randy D. Gascoyne, T. M. Grogan, Rita M. Braziel, Elias Campo, Samantha Kendrick, German Ott, Lisa M. Rimsza, Elaine S. Jaffe, Raymond R. Tubbs, Wenjun Zhang, Carlo Valentino, Wing C. Chan |
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| Rok vydání: | 2013 |
| Předmět: |
Gene Dosage
Genes myc Chromosomal translocation Biology Gene dosage Translocation Genetic Article Proto-Oncogene Proteins c-myc hemic and lymphatic diseases Gene expression Antineoplastic Combined Chemotherapy Protocols medicine Humans RNA Messenger CISH Cyclophosphamide In Situ Hybridization In Situ Hybridization Fluorescence Oncogene Germinal center General Medicine DNA Neoplasm medicine.disease Molecular biology Lymphoma Survival Rate Doxorubicin Tissue Array Analysis Vincristine Multigene Family Cancer research Prednisone Colorimetry Lymph Nodes Lymphoma Large B-Cell Diffuse Diffuse large B-cell lymphoma Signal Transduction |
| Zdroj: | American journal of clinical pathology. 139(2) |
| ISSN: | 1943-7722 |
| Popis: | Abnormalities of the MYC oncogene on chromosome 8 are characteristic of Burkitt lymphoma and other aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We recently described a colorimetric in situ hybridization (CISH) method for detecting extra copies of the MYC gene in DLBCL and the frequent occurrence of excess copies of discrete MYC signals in the context of diploidy or polyploidy of chromosome 8, which correlated with increased mRNA signals. We further observed enlarged MYC signals, which were counted as a single gene copy but, by their dimension and unusual shape, likely consisted of “clusters” of MYC genes. In this study, we sought to further characterize these clusters of MYC signals by determining whether the presence of these correlated with other genetic features, mRNA levels, protein, and overall survival. We found that MYC clusters correlated with an abnormal MYC locus and with increased mRNA. MYC mRNA correlated with protein levels, and both increased mRNA and protein correlated with poorer overall survival. MYC clusters were seen in both the germinal center and activated B-cell subtypes of DLBCL. Clusters of MYC signals may be an underappreciated, but clinically important, feature of aggressive B-cell lymphomas with potential prognostic and therapeutic relevance. |
| Databáze: | OpenAIRE |
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