History.md
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+
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+## History
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+
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+```mermaid
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+%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%%
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+timeline
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+ title Publication timing
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+ 1992-01-01 : Tanaka : DLBCL
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+ 2011-07-27 : Morin : FL
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+ 2021-04-01 : Sarkozy : PMBL
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+ 2022-07-06 : Burkhardt : BL
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+```
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\ No newline at end of file
Overview.md
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+## Overview
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+
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+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.
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+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.
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+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.
Template.md
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+---
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+bibliography: 'morinlab.bib'
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+csl: 'NLM.csl'
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+link-citations: true
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+---
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+# BCL2
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+
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+[[include:Overview.md]]
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+
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+[[include:History.md]]
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+
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+## Relevance tier by entity
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+
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+|Entity|Tier|Description |
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+|:------:|:----:|--------------------------------------|
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+|![DLBCL](images/icons/DLBCL_tier1.png) |1[@balSuperenhancerHypermutationAlters2022] |high-confidence DLBCL gene [@tanakaFrequentIncidenceSomatic1992]|
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+|![FL](images/icons/FL_tier1.png) |1 |high-confidence FL gene|
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+|![PMBL](images/icons/PMBL_tier2.png)|2|relevance in PMBL/cHL/GZL not firmly established[@sarkozyMutationalLandscapeGray2021]|
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+|![BL](images/icons/BL_tier2.png) |2 |relevance in BL not firmly established[@burkhardtClinicalRelevanceMolecular2022]|
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+ |
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+
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+## Mutation incidence in large patient cohorts (GAMBL reanalysis)
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+
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+[[include:DLBCL_BCL2.md]]
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+[[include:FL_BCL2.md]]
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+[[include:BL_BCL2.md]]
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+
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+
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+## Mutation pattern and selective pressure estimates
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+
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+|Entity|aSHM|Significant selection|dN/dS (missense)|dN/dS (nonsense)|
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+|:------:|:----:|:---------------------:|:----------------:|:----------------:|
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+|BL |Yes |No |0.000 |0 |
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+|DLBCL |Yes |Yes |2.645 |0 |
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+|FL |Yes |No |1.197 |0 |
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+
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+## aSHM regions
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+
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+|chr_name|hg19_start|hg19_end|region |regulatory_comment|
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+|:--------:|:----------:|:--------:|:---------------------------------------------------------------------------------------------:|:------------------:|
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+|chr18 |60796984 |60814103|[intron](https://genome.ucsc.edu/s/rdmorin/GAMBL%20hg19?position=chr18%3A60796984%2D60814103)|strong_enhancer |
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+|chr18 |60982728 |60988342|[TSS](https://genome.ucsc.edu/s/rdmorin/GAMBL%20hg19?position=chr18%3A60982728%2D60988342) |active_promoter |
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+
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+
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+
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+## BCL2 Hotspots
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+
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+| Chromosome |Coordinate (hg19) | ref>alt | HGVSp |
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+ | :---:| :---: | :--: | :---: |
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+| chr18 | 60985854 | T>C | M16V |
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+| chr18 | 60985854 | T>A | M16L |
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+| chr18 | 60985853 | A>T | M16K |
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+| chr18 | 60985852 | C>T | M16I |
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+| chr18 | 60985849 | C>G | K17N |
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+| chr18 | 60985842 | G>A | H20Y |
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+| chr18 | 60985840 | A>C | H20Q |
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+| chr18 | 60985838 | T>G | Y21S |
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+| chr18 | 60985835 | T>C | K22R |
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+| chr18 | 60985834 | CT>TC | K22R |
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+
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+View coding variants in ProteinPaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/BCL2_protein.html) or [hg38](https://morinlab.github.io/LLMPP/GAMBL/BCL2_protein_hg38.html)
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+
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+![](images/proteinpaint/BCL2_NM_000633.svg)
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+
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+View all variants in GenomePaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/BCL2.html) or [hg38](https://morinlab.github.io/LLMPP/GAMBL/BCL2_hg38.html)
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+
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+![](images/proteinpaint/BCL2.svg)
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+
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+
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+## BCL2 Expression
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+![](images/gene_expression/BCL2_by_pathology.svg)
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+
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+<!-- ORIGIN: 1339299 -->
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+<!-- FL: morinFrequentMutationHistonemodifying2011 -->
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+<!-- BL: burkhardtClinicalRelevanceMolecular2022b -->
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+<!-- BL: burkhardtClinicalRelevanceMolecular2022b -->
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+<!-- DLBCL: tanakaFrequentIncidenceSomatic1992 -->