Candidate genes of Waldenström’s macroglobulinemia: current evidence and research

Figures & data

Table 1 Outline of the most frequently occurring genetic aberrancies in Waldenström macroglobulinemia (WM) with an emphasis on targeted genes

Chromosomal abnormality	Encoded protein	Incidence	Function	Comments
SNM 3p22.2	MYD88	90%	Activator of canonical NF-κB	• Non-conservative, missense, gain of function, mutation in codon 265 (L265)
				• Identified via whole genome sequencing
+3	Unknown, possibly BCL6	10%	Unknown	• Shared with MZL, CLL, and MM
+4	Unknown	10%–20%	Unknown	• Familial studies suggest candidate gene to map on 4q33–4q34
				• Specific for WM
				• Occasionally the only genetic mutation
+6p	Unknown	17%	Unknown	• Occurs concomitantly with −6q
6q−		40%–50%		• Del6q discriminates WM from IgM-MGUS
Locus 21	Blimp1		Transcription repressor	• Occurs commonly in MM and NHL
Locus 23	TNFAIP3		Ubiquitin-editing enzyme
7q−	Unknown	7%		• Shared with MZL, CLL, and MM
11q−	Possibly ATM	10%	Serine-threonine kinase. Activates P53, leading to DNA repair, cell cycle arrest, and apoptosis	• Shared with MZL, CLL, and MM
13q14−	miR 15A and 16–1	10%–13%	Target proteins involved in cell cycle, proliferation and anti-apoptosis	• Shared with MZL, CLL, and MM
14q32−	TRAF3	5%	Inhibitor of noncanonical NF-κB
17p13−	P53	8%	DNA repairer, cell cycle arrester, and apoptosis generator	• Associated with shortened DFS but not OS
+18	BCL2, Malt1	15%	Anti-apoptotic, NF-κB activator	• Shared with MZL, CLL, and MM
				• Often associated with +4

Abbreviations: ATM, ataxia telangiectasia mutated; CLL, chronic lymphocytic leukemia; DFS, disease-free survival; Ig, immunoglobulin; MGUS, monoclonal gammopathy of unknown significance; MM, multiple myeloma; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; OS, overall survival; SNM, single-nucleotide mutation.