Table 2.

Genetic lesions in FL

Functional categoryGeneApproximate frequency of mutated cases, %*Proposed functional consequencesSelected references
Apoptosis BCL2 80-90† Rescue from apoptosis in the GC 5,6  
Histone modification KMT2D (MLL2) 60-90 Reduced H3K4 methylation, promotion of GC B-cell proliferation 67,71,76  
CREBBP 60-70 Reduced histone acetylation, enhances BCL6 function, impaired TP53 function 71,75  
EP300 10-20 Reduced histone acetylation 71,75  
EZH2 20-30 Increased bi- and trimethylation of H3K27, reduced expression of target genes 70,81  
HIST1H1B-E and other HIST1 members 30-40 Unclear 68,69  
Nucleosome remodeling ARID1A 10-15 Alteration of chromatin remodeling, specific consequences unclear 69,82  
BCL7A ∼10 Alteration of chromatin remodeling, specific consequences unclear 68  
Signaling CARD11 10-15 Activation of NF-κB signaling 68,82  
RRAGC 15-20 mTORC1 activation, promotes cellular metabolism and growth 68,73  
GNA13 ∼10 Inactivating mutations promote B-cell growth and lymphoma cell dissemination 71  
TNFRSF14 30-40 Loss-of-function mutations may prevent inhibitory HVEM signaling 87,88  
SESTRIN1 ∼20‡ Inactivating mutations promote mTOR activity 74  
Transcription factors MEF2B 10-20 Enforced activity of BCL6 82,83  
FOXO1 ∼10 Mutations cause nuclear retention, maintains dark-zone B-cell program, cooperates with BCL6 82,84  
STAT6 10-15 Hyperactivation of JAK/STAT signaling 77  
Functional categoryGeneApproximate frequency of mutated cases, %*Proposed functional consequencesSelected references
Apoptosis BCL2 80-90† Rescue from apoptosis in the GC 5,6  
Histone modification KMT2D (MLL2) 60-90 Reduced H3K4 methylation, promotion of GC B-cell proliferation 67,71,76  
CREBBP 60-70 Reduced histone acetylation, enhances BCL6 function, impaired TP53 function 71,75  
EP300 10-20 Reduced histone acetylation 71,75  
EZH2 20-30 Increased bi- and trimethylation of H3K27, reduced expression of target genes 70,81  
HIST1H1B-E and other HIST1 members 30-40 Unclear 68,69  
Nucleosome remodeling ARID1A 10-15 Alteration of chromatin remodeling, specific consequences unclear 69,82  
BCL7A ∼10 Alteration of chromatin remodeling, specific consequences unclear 68  
Signaling CARD11 10-15 Activation of NF-κB signaling 68,82  
RRAGC 15-20 mTORC1 activation, promotes cellular metabolism and growth 68,73  
GNA13 ∼10 Inactivating mutations promote B-cell growth and lymphoma cell dissemination 71  
TNFRSF14 30-40 Loss-of-function mutations may prevent inhibitory HVEM signaling 87,88  
SESTRIN1 ∼20‡ Inactivating mutations promote mTOR activity 74  
Transcription factors MEF2B 10-20 Enforced activity of BCL6 82,83  
FOXO1 ∼10 Mutations cause nuclear retention, maintains dark-zone B-cell program, cooperates with BCL6 82,84  
STAT6 10-15 Hyperactivation of JAK/STAT signaling 77  

Adapted from Weigert and Weinstock.78 

HVEM, herpesvirus entry mediator; mTOR, mammalian target of rapamycin.

*

The table is restricted to genetic lesions that are estimated to occur in at least 10% of cases of FL.

†

Frequency of IGH-BCL2 translocations.

‡

Homozygous or heterozygous deletions at Chr6q21 that involve the SESTRIN1 gene.

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