---
bibliography: 'morinlab.bib'
csl: 'NLM.csl'
link-citations: true
nocite: |
  @balSuperenhancerHypermutationAlters2022, @tanakaFrequentIncidenceSomatic1992, @sarkozyMutationalLandscapeGray2021, @burkhardtClinicalRelevanceMolecular2022
---

[[_TOC_]]

## Overview

BCL2 mutations are frequently found in DLBCL, particularly in the germinal center B-cell (GCB) subtype, and are often located in the flexible loop domain and outside the BCL2-homology domains. 
These mutations are caused by the somatic hypermutation process. The presence of these mutations are strongly correlated with the presence of a translocation between BCL2 and one of the immunoglobulin loci.
Although missense mutations may not be under positive selective pressure in the context of lymphomagenesis, some of these mutations may interfere with the function of BCL2 antagonists.


## Relevance tier by entity

[[include:table1_BCL2.md]]

## Mutation incidence in large patient cohorts (GAMBL reanalysis)

[[include:DLBCL_BCL2.md]]
[[include:FL_BCL2.md]]
[[include:BL_BCL2.md]]

## Mutation pattern and selective pressure estimates

[[include:dnds_BCL2.md]]

## aSHM regions

[[include:ashm_BCL2.md]]

## BCL2 Hotspots

| Chromosome |Coordinate (hg19) | ref>alt | HGVSp | 
 | :---:| :---: | :--: | :---: |
| chr18 | 60985854 | T>C | M16V |
| chr18 | 60985854 | T>A | M16L |
| chr18 | 60985853 | A>T | M16K |
| chr18 | 60985852 | C>T | M16I |
| chr18 | 60985849 | C>G | K17N |
| chr18 | 60985842 | G>A | H20Y |
| chr18 | 60985840 | A>C | H20Q |
| chr18 | 60985838 | T>G | Y21S |
| chr18 | 60985835 | T>C | K22R |
| chr18 | 60985834 | CT>TC | K22R |

[[include:browser_BCL2.md]]

## Expression
![](images/gene_expression/BCL2_by_pathology.svg)

<!-- ORIGIN: 1339299 -->
<!-- FL: morinFrequentMutationHistonemodifying2011 -->
<!-- BL: burkhardtClinicalRelevanceMolecular2022b -->
<!-- BL: burkhardtClinicalRelevanceMolecular2022b -->
<!-- DLBCL: tanakaFrequentIncidenceSomatic1992 -->

[[include:mermaid_BCL2.md]]

## References