Document Detail

Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma.
MedLine Citation:
PMID:  23355209     Owner:  NLM     Status:  MEDLINE    
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of clinical pathology     Volume:  139     ISSN:  1943-7722     ISO Abbreviation:  Am. J. Clin. Pathol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-03-19     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  0370470     Medline TA:  Am J Clin Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  242-54     Citation Subset:  AIM; IM    
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cyclophosphamide / therapeutic use
DNA, Neoplasm / analysis
Doxorubicin / therapeutic use
Gene Dosage
Genes, myc*
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
Grant Support
P50 CA130805/CA/NCI NIH HHS; T32 CA009213/CA/NCI NIH HHS; U01 CA157581/CA/NCI NIH HHS
Reg. No./Substance:
0/DNA, Neoplasm; 0/Proto-Oncogene Proteins c-myc; 0/RNA, Messenger; 57-22-7/Vincristine; 80168379AG/Doxorubicin; 8N3DW7272P/Cyclophosphamide; VB0R961HZT/Prednisone

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