Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma.

Abstract

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.

• Authors: Carlo Valentino, Samantha Kendrick, Nathalie Johnson, Randy Gascoyne, Wing C Chan, Dennis Weisenburger, Rita Braziel, James R Cook, Raymond Tubbs, Elias Campo, Andreas Rosenwald, German Ott, Jan Delabie, Elaine Jaffe, Wenjun Zhang, Patrick Brunhoeber, Hiro Nitta, Tom Grogan, Lisa Rimsza
• Journal: American journal of clinical pathology (Am J Clin Pathol) Vol. 139 Issue 2 Pg. 242-54 (Feb 2013) ISSN: 1943-7722 [Electronic] England
• PMID: 23355209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• Proto-Oncogene Proteins c-myc
• RNA, Messenger
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Colorimetry
• Cyclophosphamide (therapeutic use)
• DNA, Neoplasm (analysis)
• Doxorubicin (therapeutic use)
• Gene Dosage
• Genes, myc
• Humans
• In Situ Hybridization (methods)
• In Situ Hybridization, Fluorescence
• Lymph Nodes (metabolism, pathology)
• Lymphoma, Large B-Cell, Diffuse (drug therapy, genetics, mortality, pathology)
• Multigene Family
• Prednisone (therapeutic use)
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• RNA, Messenger (genetics)
• Signal Transduction
• Survival Rate
• Tissue Array Analysis
• Translocation, Genetic
• Vincristine (therapeutic use)