Molecular prognostic factors in FL associated with prognosis
| Factor . | Role/function . | Mutation/alteration (if applicable) . | Consequence and prognostic impact . | Reference . |
|---|---|---|---|---|
| Microenvironment | Gene signatures were developed from whole-genome microarrays of frozen lymph node biopsies of untreated FL patients yielding IR1 and IR2 | NA | IR1: overexpression of genes enriched for T cells; favorable, RR of death, 0.15; 95% CI, 0.05-0.46. IR2: overexpression of genes expressed in follicular dendritic cells and macrophages; unfavorable, RR of death, 9.35; 95% CI, 3.02-28.90. | 10 |
| MLL2 | Histone methyltransferase; acts as a tumor suppressor | Inactivating mutation; found in 89% of FL | May contribute to FL tumorigenesis | 43 |
| CREBBP | Histone acetyltransferase; functions as transcriptional co-activator; mutation found in ∼32% of FL | Inactivating mutation removes or inactivates coding domains | Failure to acetylate BCL6 and p53; constitutive activation of bcl-6 and decrease in p53 activity | 44 |
| EP300 | Histone acetyltransferase; functions as transcriptional co-activator; mutation found in ∼9% of FL | |||
| ARID1A | Histone linker, chromatin modifier, and tumor suppressor | Inactivating mutation; found in 11% of FL | Impaired DNA repair; correlates with longer FFS | 43,51,52 |
| MEF2B | Histone methyltransferase; cooperates with CREBBP and EP300; activates transcription of BCL6 | Inactivating mutation; found in 7% to 15% of FL | Enhanced transcriptional activity of MEF2B deregulates BCL6 expression and contributes to lymphomagenesis | 43 |
| EZH2 | Histone methyltransferase; promotes normal germinal center development | Activating, gain of function mutation; occurs in ∼7% to 30% of FL. Seems to be an early event in FL pathogenesis | Causes elevated H3K27 trimethylation, promotes follicular hyperplasia, contributes to pathogenesis of lymphoma | 43,48,53,54 |
| BCL2 | Antiapoptotic protein; present at both diagnosis and at transformation in FL | Gain of function mutations; affecting 16% to 65% of FL | Increased risk of transformation and poor survival | 33 |
| Factor . | Role/function . | Mutation/alteration (if applicable) . | Consequence and prognostic impact . | Reference . |
|---|---|---|---|---|
| Microenvironment | Gene signatures were developed from whole-genome microarrays of frozen lymph node biopsies of untreated FL patients yielding IR1 and IR2 | NA | IR1: overexpression of genes enriched for T cells; favorable, RR of death, 0.15; 95% CI, 0.05-0.46. IR2: overexpression of genes expressed in follicular dendritic cells and macrophages; unfavorable, RR of death, 9.35; 95% CI, 3.02-28.90. | 10 |
| MLL2 | Histone methyltransferase; acts as a tumor suppressor | Inactivating mutation; found in 89% of FL | May contribute to FL tumorigenesis | 43 |
| CREBBP | Histone acetyltransferase; functions as transcriptional co-activator; mutation found in ∼32% of FL | Inactivating mutation removes or inactivates coding domains | Failure to acetylate BCL6 and p53; constitutive activation of bcl-6 and decrease in p53 activity | 44 |
| EP300 | Histone acetyltransferase; functions as transcriptional co-activator; mutation found in ∼9% of FL | |||
| ARID1A | Histone linker, chromatin modifier, and tumor suppressor | Inactivating mutation; found in 11% of FL | Impaired DNA repair; correlates with longer FFS | 43,51,52 |
| MEF2B | Histone methyltransferase; cooperates with CREBBP and EP300; activates transcription of BCL6 | Inactivating mutation; found in 7% to 15% of FL | Enhanced transcriptional activity of MEF2B deregulates BCL6 expression and contributes to lymphomagenesis | 43 |
| EZH2 | Histone methyltransferase; promotes normal germinal center development | Activating, gain of function mutation; occurs in ∼7% to 30% of FL. Seems to be an early event in FL pathogenesis | Causes elevated H3K27 trimethylation, promotes follicular hyperplasia, contributes to pathogenesis of lymphoma | 43,48,53,54 |
| BCL2 | Antiapoptotic protein; present at both diagnosis and at transformation in FL | Gain of function mutations; affecting 16% to 65% of FL | Increased risk of transformation and poor survival | 33 |
CI, confidence interval; FFS, failure-free survival; IR, immune response; NA, not applicable; RR, relative risk.