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 & LYMPHOMA Cerhan, J. R., Natkunam, Y., Morton, L. M., Maurer, M. J., Asmann, Y., Habermann, T. M., Vasef, M. A., Cozen, W., Lynch, C. F., Allmer, C., Slager, S. L., Lossos, I. S., Chanock, S. J., Rothman, N., Hartge, P., Dogan, A., Wang, S. S. 2012; 53 (6): 1105-1112

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.

View details for DOI 10.3109/10428194.2011.638717

View details for Web of Science ID 000304311500016

View details for PubMedID 22066713

View details for PubMedCentralID PMC3575512