Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma

Christopher J. Stasik, Hiroaki Nitta, Wenjun Zhang, Charles H. Mosher, James R. Cook, Raymond R. Tubbs, Joseph M. Unger, Tracy A. Brooks, Daniel O. Persky, Sarah T. Wilkinson, Thomas M. Grogan, Lisa M Rimsza

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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. Design and 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.

Original languageEnglish (US)
Pages (from-to)597-603
Number of pages7
JournalHaematologica
Volume95
Issue number4
DOIs
StatePublished - Apr 2010

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Gene Dosage
Lymphoma, Large B-Cell, Diffuse
Messenger RNA
Chromosomes, Human, Pair 8
Centromere
Genes
In Situ Hybridization
Color

Keywords

  • Large B cell lymphoma
  • mRNA
  • MYC gene

ASJC Scopus subject areas

  • Hematology

Cite this

Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma. / Stasik, Christopher J.; Nitta, Hiroaki; Zhang, Wenjun; Mosher, Charles H.; Cook, James R.; Tubbs, Raymond R.; Unger, Joseph M.; Brooks, Tracy A.; Persky, Daniel O.; Wilkinson, Sarah T.; Grogan, Thomas M.; Rimsza, Lisa M.

In: Haematologica, Vol. 95, No. 4, 04.2010, p. 597-603.

Research output: Contribution to journalArticle

Stasik, CJ, Nitta, H, Zhang, W, Mosher, CH, Cook, JR, Tubbs, RR, Unger, JM, Brooks, TA, Persky, DO, Wilkinson, ST, Grogan, TM & Rimsza, LM 2010, 'Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma', Haematologica, vol. 95, no. 4, pp. 597-603. https://doi.org/10.3324/haematol.2009.012864
Stasik, Christopher J. ; Nitta, Hiroaki ; Zhang, Wenjun ; Mosher, Charles H. ; Cook, James R. ; Tubbs, Raymond R. ; Unger, Joseph M. ; Brooks, Tracy A. ; Persky, Daniel O. ; Wilkinson, Sarah T. ; Grogan, Thomas M. ; Rimsza, Lisa M. / Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma. In: Haematologica. 2010 ; Vol. 95, No. 4. pp. 597-603.
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T1 - Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma

AU - Stasik, Christopher J.

AU - Nitta, Hiroaki

AU - Zhang, Wenjun

AU - Mosher, Charles H.

AU - Cook, James R.

AU - Tubbs, Raymond R.

AU - Unger, Joseph M.

AU - Brooks, Tracy A.

AU - Persky, Daniel O.

AU - Wilkinson, Sarah T.

AU - Grogan, Thomas M.

AU - Rimsza, Lisa M

PY - 2010/4

Y1 - 2010/4

N2 - 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. Design and 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.

AB - 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. Design and 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.

KW - Large B cell lymphoma

KW - mRNA

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