LIM domain only 2 protein expression, LMO2 germline genetic variation, and overall survival in diffuse large B-cell lymphoma in the pre-rituximab era

James R. Cerhan, Yasodha Natkunam, Lindsay M. Morton, Matthew J. Maurer, Yan Asmann, Thomas M. Habermann, Mohammad A. Vasef, Wendy Cozen, Charles F. Lynch, Cristine Allmer, Susan L. Slager, Izidore Lossos, Stephen J. Chanock, Nathaniel Rothman, Patricia Hartge, Ahmet Dogan, Sophia S. Wang

Research output: Contribution to journalArticle

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Abstract

Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] 0.55; 95% confidence interval [CI] 0.310.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p 0.02). Compared to a model with clinical factors only (c-statistic 0.676), adding the four SNPs (c-statistic 0.751) or LMO2 IHC (c-statistic 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status.

Original languageEnglish
Pages (from-to)1105-1112
Number of pages8
JournalLeukemia and Lymphoma
Volume53
Issue number6
DOIs
StatePublished - Jun 1 2012

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LIM Domain Proteins
Lymphoma, Large B-Cell, Diffuse
Immunohistochemistry
Single Nucleotide Polymorphism
Rituximab
Confidence Intervals
Biopsy
Messenger RNA
DNA

Keywords

  • Diffuse large B-cell lymphoma
  • LMO2
  • Prognosis
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

LIM domain only 2 protein expression, LMO2 germline genetic variation, and overall survival in diffuse large B-cell lymphoma in the pre-rituximab era. / Cerhan, James R.; Natkunam, Yasodha; Morton, Lindsay M.; Maurer, Matthew J.; Asmann, Yan; Habermann, Thomas M.; Vasef, Mohammad A.; Cozen, Wendy; Lynch, Charles F.; Allmer, Cristine; Slager, Susan L.; Lossos, Izidore; Chanock, Stephen J.; Rothman, Nathaniel; Hartge, Patricia; Dogan, Ahmet; Wang, Sophia S.

In: Leukemia and Lymphoma, Vol. 53, No. 6, 01.06.2012, p. 1105-1112.

Research output: Contribution to journalArticle

Cerhan, JR, Natkunam, Y, Morton, LM, Maurer, MJ, Asmann, Y, Habermann, TM, Vasef, MA, Cozen, W, Lynch, CF, Allmer, C, Slager, SL, Lossos, I, Chanock, SJ, Rothman, N, Hartge, P, Dogan, A & Wang, SS 2012, 'LIM domain only 2 protein expression, LMO2 germline genetic variation, and overall survival in diffuse large B-cell lymphoma in the pre-rituximab era', Leukemia and Lymphoma, vol. 53, no. 6, pp. 1105-1112. https://doi.org/10.3109/10428194.2011.638717
Cerhan, James R. ; Natkunam, Yasodha ; Morton, Lindsay M. ; Maurer, Matthew J. ; Asmann, Yan ; Habermann, Thomas M. ; Vasef, Mohammad A. ; Cozen, Wendy ; Lynch, Charles F. ; Allmer, Cristine ; Slager, Susan L. ; Lossos, Izidore ; Chanock, Stephen J. ; Rothman, Nathaniel ; Hartge, Patricia ; Dogan, Ahmet ; Wang, Sophia S. / LIM domain only 2 protein expression, LMO2 germline genetic variation, and overall survival in diffuse large B-cell lymphoma in the pre-rituximab era. In: Leukemia and Lymphoma. 2012 ; Vol. 53, No. 6. pp. 1105-1112.
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abstract = "Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] 0.55; 95{\%} confidence interval [CI] 0.310.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p 0.02). Compared to a model with clinical factors only (c-statistic 0.676), adding the four SNPs (c-statistic 0.751) or LMO2 IHC (c-statistic 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status.",
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AU - Maurer, Matthew J.

AU - Asmann, Yan

AU - Habermann, Thomas M.

AU - Vasef, Mohammad A.

AU - Cozen, Wendy

AU - Lynch, Charles F.

AU - Allmer, Cristine

AU - Slager, Susan L.

AU - Lossos, Izidore

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Hartge, Patricia

AU - Dogan, Ahmet

AU - Wang, Sophia S.

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N2 - Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] 0.55; 95% confidence interval [CI] 0.310.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p 0.02). Compared to a model with clinical factors only (c-statistic 0.676), adding the four SNPs (c-statistic 0.751) or LMO2 IHC (c-statistic 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status.

AB - Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] 0.55; 95% confidence interval [CI] 0.310.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p 0.02). Compared to a model with clinical factors only (c-statistic 0.676), adding the four SNPs (c-statistic 0.751) or LMO2 IHC (c-statistic 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status.

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