High grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements: unraveling the genetic landscape of a rare aggressive subtype of non-Hodgkin lymphoma

Figures & data

Table 1. Patient characteristics.

Patient ID	Sex	Age	Clone %	Diagnosis	Ki-67	HITs	MYC IHC	BCL2 IHC/FISH	BCL6 IHC/FISH	FFPE/ BM	Microarry (CNA)	Lymphoma panel	SNV/Indel
1	M	71	90%	DLBCL	70%	Double	−	+/rearr	+/wt	BM	SNP array	Yes	7
2	M	57	70%	DLBCL	80%	Triple	n.a.	+/rearr	+/rearr	FFPE	ONCOSCAN	Yes	8
3	M	62	50%	DLBCL-GCB	80%	Triple	50%	+/rearr	+/rearr	FFPE	ONCOSCAN	Yes	8
4	F	61	60%	DLBCL-GCB	n.a.	Triple	15%	+/rearr	+/rearr	FFPE	n.a.	Yes	7
5	M	56	50%	FL	20%	Double	30%	+/rearr	+/wt	FFPE	ONCOSCAN	Yes	7
6	M	82	80%	DLBCL*	90%	Double	90%	+weak/rearr	+partial/wt	FFPE	ONCOSCAN	Yes	11
7	F	69	>90%	DLBCL-GCB	95%	Double	90%	+/rearr	+/wt	FFPE	ONCOSCAN	Yes	5

M: male; F: female; DLBCL: diffuse large B-cell lymphoma; DLBCL-GCB: diffuse large B-cell lymphoma Germinal Center; FL: Follicular lymphoma; B, n.a.: not available, +, positive, −, negative, rear: the presence of rearrangement; wt: absence of rearrangement; FFPE: formalin-fixed paraffin-embedded; BM: bone marrow; CNA: copy number abnormalities; SNV: Single nucleotide variant. *previous diagnosis of follicular lymphoma.

Figure 1. High grade B-cell lymphoma mutational landscape. (A) Gene mutation number (N) observed sequencing 54 genes in 7 patients with high-grade B-cell lymphoma. (B) Frequency of detected gene mutations in two different high-grade B-cell lymphoma subtypes: Double Hit (blue) and Triple Hit (grey). (C) Heat-map of 7 patients detected mutations across Double Hit (DH) and Triple Hit (TH) subtypes.

Figure 2. Genetic profiling of BCL2, MYC and FOXO1 genes. (A) BCL2 protein diagram, domain annotations and the position of the nine detected missense mutations; 85.7% of patients carried BCL2 mutations. Bcl-2 homology 1, 2, 3 and 4 domains (BH1, BH2, BH3 and BH4). (B) MYC protein diagram, domain annotations and site of the three found somatic variants (42.9% of patients). (C) FOXO1 protein diagram, domain annotations and site of the four found somatic variants.