Abstract

Recently whole-exome-sequencing has identified oncogenic BRAF and KRAS mutations as likely drivers in diffuse-large B-cell lymphoma (DLBCL). It is currently unclear whether primary mediastinal B-cell lymphoma (PMBL), a clinicopathologically distinct variant of diffuse-large B-cell lymphoma, harbors such mutations. Here, we screened 100 samples (84 primary tumors and 16 cell lines), composed of 52 PMBL and 48 DLBCL samples for BRAF (V600/601) and KRAS (G12-K16) hotspot mutations using a sensitive pyrosequencing approach. All 100 samples were BRAF and KRAS wild-type. When combining our results with those reported in the literature (Table 1), the overall mutation frequency in DLBCL for BRAF is ∼2.4% (n=13/541) and for KRAS is ∼1.6% (n=7/445). We demonstrate the absence of BRAF and KRAS hotspot mutations in PMBL. The overall prevalence of KRAS and BRAF mutations argues against hotspot genotyping as part of the diagnostic workup in PMBL/DLBCL.

Table 1

Summary of DLBCL genotyping results

 BRAF KRAS 
 Mut./tested % Mut./tested % 
Lohr et al., 2011 2/55 4,1 2/55 4,1 
Pasqualucci et al., 2011 0/48 0/48 
COSMIC* 11/338 3.2 5/242 2,0 
Subtotal 13/441 3.0 7/345 2.0 
Nagel et al., (here) 0/100 0/100 
Summary 13/541 2,4 7/445 1,6% 
 BRAF KRAS 
 Mut./tested % Mut./tested % 
Lohr et al., 2011 2/55 4,1 2/55 4,1 
Pasqualucci et al., 2011 0/48 0/48 
COSMIC* 11/338 3.2 5/242 2,0 
Subtotal 13/441 3.0 7/345 2.0 
Nagel et al., (here) 0/100 0/100 
Summary 13/541 2,4 7/445 1,6% 

*At time of review, COSMIC did not include the results from Lohr et al. and Pasqualucci et al.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.