title: Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma.
abstract: BACKGROUND
  Translocations involving the MYC gene and increased MYC mRNA levels are associated with poor outcome in diffuse large B-cell lymphoma. However, the presence of increased MYC gene copy number and/or polysomy of chromosome 8 have not been previously described.
  
  
  METHODS
  Utilizing dual color chromogenic in situ hybridization, we investigated MYC gene copy and chromosome 8 centromere numbers in 52 cases of diffuse large B-cell lymphoma. Cases were divided into those with "increased" or "not increased" MYC gene copy number for comparison with MYC mRNA levels, Ki-67 values, and survival.
  
  
  RESULTS
  Increased MYC gene copy number was present in 38% of cases. Overall, the average MYC mRNA level was 2398 (range, 342 - 9783) and the percentage of nuclei positive for Ki-67 was 57.5% (range, 20-87%). Within the group with increased MYC copy number, the MYC mRNA values ranged from 816 to 5912 (average, 2843) and the Ki-67 values ranged from 23% to 83% (average, 57%). Within the group with not increased MYC copy number, MYC mRNA values ranged from 342 to 9783 (average, 2118) and the Ki-67 values ranged from 20% to 87% (average, 58%). There was a statistically significant relationship between increased MYC gene copy number and increased MYC mRNA (P=0.034) and a trend toward a relationship between increased mRNA and higher Ki-67 values.
  
  
  CONCLUSIONS
  This is the first report that low level copy number increases are common in diffuse large B-cell lymphoma and that these changes correlate with MYC mRNA in a statistically significant manner. MYC copy number changes are an additional possible molecular mechanism that may result in increased mRNA and, likely, high proliferation and poor outcome.
authors.affiliation: Department of Pathology, University of Arizona, 1501 N Campbell Avenue, PO Box 245043, Tucson, AZ 85724-5043, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Stasik
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nitta
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
authors.forename: Charles H
authors.initials: CH
authors.lastname: Mosher
authors.forename: James R
authors.initials: JR
authors.lastname: Cook
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Unger
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Brooks
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Persky
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Wilkinson
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
mesh_terms: D049109:Cell Proliferation; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005784:Gene Amplification; D018628:Gene Dosage; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014178:Translocation, Genetic
chemical_list: D019394:Ki-67 Antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger