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

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 M Rimsza

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)242-254
Number of pages13
JournalAmerican Journal of Clinical Pathology
Volume139
Issue number2
DOIs
StatePublished - Feb 2013

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Lymphoma, Large B-Cell, Diffuse
Multigene Family
In Situ Hybridization
B-Cell Lymphoma
Messenger RNA
Chromosomes, Human, Pair 8
Proteins
Polyploidy
Germinal Center
Burkitt Lymphoma
Diploidy
Oncogenes
Genes
B-Lymphocytes

Keywords

  • Colorimetric
  • Gene expression
  • Immunohistochemistry
  • In situ hybridization
  • Lymphoma
  • MYC
  • Ploidy
  • Survival

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large b-cell lymphoma. / Valentino, Carlo; Kendrick, Samantha; Johnson, Nathalie; Gascoyne, Randy; Chan, Wing C.; Weisenburger, Dennis; Braziel, Rita; Cook, James R.; Tubbs, Raymond; Campo, Elias; Rosenwald, Andreas; Ott, German; Delabie, Jan; Jaffe, Elaine; Zhang, Wenjun; Brunhoeber, Patrick; Nitta, Hiro; Grogan, Tom; Rimsza, Lisa M.

In: American Journal of Clinical Pathology, Vol. 139, No. 2, 02.2013, p. 242-254.

Research output: Contribution to journalArticle

Valentino, C, Kendrick, S, Johnson, N, Gascoyne, R, Chan, WC, Weisenburger, D, Braziel, R, Cook, JR, Tubbs, R, Campo, E, Rosenwald, A, Ott, G, Delabie, J, Jaffe, E, Zhang, W, Brunhoeber, P, Nitta, H, Grogan, T & Rimsza, LM 2013, 'Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large b-cell lymphoma', American Journal of Clinical Pathology, vol. 139, no. 2, pp. 242-254. https://doi.org/10.1309/AJCP2Z0TAGMUYJEB
Valentino, Carlo ; Kendrick, Samantha ; Johnson, Nathalie ; Gascoyne, Randy ; Chan, Wing C. ; Weisenburger, Dennis ; Braziel, Rita ; Cook, James R. ; Tubbs, Raymond ; Campo, Elias ; Rosenwald, Andreas ; Ott, German ; Delabie, Jan ; Jaffe, Elaine ; Zhang, Wenjun ; Brunhoeber, Patrick ; Nitta, Hiro ; Grogan, Tom ; Rimsza, Lisa M. / Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large b-cell lymphoma. In: American Journal of Clinical Pathology. 2013 ; Vol. 139, No. 2. pp. 242-254.
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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.",
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AU - Valentino, Carlo

AU - Kendrick, Samantha

AU - Johnson, Nathalie

AU - Gascoyne, Randy

AU - Chan, Wing C.

AU - Weisenburger, Dennis

AU - Braziel, Rita

AU - Cook, James R.

AU - Tubbs, Raymond

AU - Campo, Elias

AU - Rosenwald, Andreas

AU - Ott, German

AU - Delabie, Jan

AU - Jaffe, Elaine

AU - Zhang, Wenjun

AU - Brunhoeber, Patrick

AU - Nitta, Hiro

AU - Grogan, Tom

AU - Rimsza, Lisa M

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