Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma.
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.
Stasik
Christopher J
CJ
Department of Pathology, University of Arizona, 1501 N Campbell Avenue, PO Box 245043, Tucson, AZ 85724-5043, USA.
Nitta
Hiroaki
H
Zhang
Wenjun
W
Mosher
Charles H
CH
Cook
James R
JR
Tubbs
Raymond R
RR
Unger
Joseph M
JM
Brooks
Tracy A
TA
Persky
Daniel O
DO
Wilkinson
Sarah T
ST
Grogan
Thomas M
TM
Rimsza
Lisa M
LM
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
D019394:Ki-67 Antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger