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

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] 0.31–0.97). 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.

Keywords::

• Diffuse large B-cell lymphoma
• LMO2
• prognosis
• single nucleotide polymorphisms

Acknowledgements

This work was supported by the National Cancer Institute (grants R01 CA96704, R01 CA129539, P50 CA97274, P01 CA17054 and P30 CA014089; NCI Intramural Program; SEER contracts N01-PC35139, N01-PC67008, N01-PC67009, N01-PC65064, N01-PC71105).

We thank Drs. Scott Davis (Fred Hutchinson Cancer Research Center) and Richard K. Severson (Wayne State University) for contributing data. The authors thank Sondra Buehler for editorial assistance.

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