title: 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.
authors: College of Medicine, Mayo Clinic, Rochester, MN, USA. cerhan.james@mayo.edu
authors: James R
authors: JR
authors: Cerhan
authors: Yasodha
authors: Y
authors: Natkunam
authors: Lindsay M
authors: LM
authors: Morton
authors: Matthew J
authors: MJ
authors: Maurer
authors: Yan
authors: Y
authors: Asmann
authors: Thomas M
authors: TM
authors: Habermann
authors: Mohammad A
authors: MA
authors: Vasef
authors: Wendy
authors: W
authors: Cozen
authors: Charles F
authors: CF
authors: Lynch
authors: Cristine
authors: C
authors: Allmer
authors: Susan L
authors: SL
authors: Slager
authors: Izidore S
authors: IS
authors: Lossos
authors: Stephen J
authors: SJ
authors: Chanock
authors: Nathaniel
authors: N
authors: Rothman
authors: Patricia
authors: P
authors: Hartge
authors: Ahmet
authors: A
authors: Dogan
authors: Sophia S
authors: SS
authors: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation / Q000502:physiology; D018095:Germ-Line Mutation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism*; D015810:Linkage Disequilibrium; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D000069283:Rituximab; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D011518:Proto-Oncogene Proteins; D000069283:Rituximab