Changes in 2a851ee: update

				genes/EZH2.md
			
          @@ -1,95 +0,0 @@

          ----

          -bibliography: 'morinlab.bib'

          -csl: 'NLM.csl'

          -link-citations: true

          -nocite: |

          -  @mottokIntegrativeGenomicAnalysis2019, @morinSomaticMutationsAltering2010, @loveGeneticLandscapeMutations2012

          ----

          -[[_TOC_]]

          -

          -## Overview

          -EZH2 encodes a histone methyltransferase that is a component of the polycomb repressive complex 2 (PRC2). 

          -This gene is recurrently mutated in both FL and DLBCL and has a common mutation hot spot (Y646) that affects the SET domain.[@morinSomaticMutationsAltering2010]

          -EZH2 mutations are one of the defining features of the EZB genetic subgroup of DLBCL.[@wrightProbabilisticClassificationTool2020] 

          -Although mutations in EZH2 have been described in some BL patients, they are extremely rare in most BL cohorts that have been sequenced.[@loveGeneticLandscapeMutations2012; @thomasGeneticSubgroupsInform2023] 

          -

          -

          -## Experimental Evidence

          -

          -Mutations at the main hotspot and some less common hotspots lead to enhanced methylation by PRC2.[@yapSomaticMutationsEZH22011]

          -A number of small molecule/pharmacologic inhibitors of EZH2 activity have been described.[@garapaty-raoIdentificationEZH2EZH12013; @knutsonSelectiveInhibitionEZH22014] At least one of these, tazemetostat, has shown benefit in FL.[@morinTreatingLymphomaNow2021] 

          -Combination therapies including EZH2 inhibitors are also under exploration for DLBCL patients with mutant EZH2.[@scholzeCombinedEZH2Bcl22020]

          -

          -

          -## Relevance tier by entity

          -

          -[[include:tables/table1_EZH2]]

          -

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

          -

          -

          -### DLBCL

          -[[include:tables/DLBCL_EZH2.md]]

          -

          -### FL

          -[[include:tables/FL_EZH2.md]]

          -

          -### BL

          -[[include:tables/BL_EZH2.md]]

          -

          -

          -## Mutation pattern and selective pressure estimates

          -

          -[[include:tables/dnds_EZH2.md]]

          -

          -## EZH2 Hotspots

          -

          -| Chromosome |Coordinate (hg19) | ref>alt | HGVSp | 

          - | :---:| :---: | :--: | :---: |

          -| chr7 | 148508745 | T>C | N640S |

          -|chr7|148508740|A>G|F642L| 

          -| chr7 | 148508728 | A>T | Y646N |

          -| chr7 | 148508728 | A>G | Y646H |

          -| chr7 | 148508727 | T>G | Y646S |

          -| chr7 | 148508727 | T>C | Y646C |

          -| chr7 | 148508727 | T>A | Y646F |

          -|chr7|148506466|TG>GC|A682G|

          -|chr7|148506467|G>C|A682G|

          -|chr7|148506437|GC>AA|A692L|

          -|chr7|148506437|G>A|A692V|

          -

          -[[include:tables/browser_EZH2.md]]

          -

          -## Expression

          -![](images/gene_expression/EZH2_by_pathology.svg)

          -

          -## Representative Mutations

          -

          -### BL

          -

          -![](primary/Love_EZH2.svg)

          -**Rating**

          -&starf; &starf; &starf; &starf; &starf;

          -

          -## All Mutations

          -

          -### BL

          -

          -[@loveGeneticLandscapeMutations2012]

          -

          -[1092](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Love/1092_reports.html)

          -[671](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Love/671_reports.html)

          -[672](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Love/672_reports.html)

          -[675](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Love/675_reports.html)

          -

          -<!-- ORIGIN: morinSomaticMutationsAltering2010 -->

          -<!-- BL: loveGeneticLandscapeMutations2012 -->

          -<!-- FL: morinSomaticMutationsAltering2010a -->

          -<!-- BL: loveGeneticLandscapeMutations2012 -->

          -<!-- DLBCL: morinSomaticMutationsAltering2010 -->

          -<!-- PMBL: mottokIntegrativeGenomicAnalysis2019b -->

          -

          -[[include:tables/mermaid_EZH2.md]]

          -

          -## References

          -

...	...	@@ -1,95 +0,0 @@
1		----
2		-bibliography: 'morinlab.bib'
3		-csl: 'NLM.csl'
4		-link-citations: true
5		-nocite: \|
6		- @mottokIntegrativeGenomicAnalysis2019, @morinSomaticMutationsAltering2010, @loveGeneticLandscapeMutations2012
7		----
8		-[[_TOC_]]
9		-
10		-## Overview
11		-EZH2 encodes a histone methyltransferase that is a component of the polycomb repressive complex 2 (PRC2).
12		-This gene is recurrently mutated in both FL and DLBCL and has a common mutation hot spot (Y646) that affects the SET domain.[@morinSomaticMutationsAltering2010]
13		-EZH2 mutations are one of the defining features of the EZB genetic subgroup of DLBCL.[@wrightProbabilisticClassificationTool2020]
14		-Although mutations in EZH2 have been described in some BL patients, they are extremely rare in most BL cohorts that have been sequenced.[@loveGeneticLandscapeMutations2012; @thomasGeneticSubgroupsInform2023]
15		-
16		-
17		-## Experimental Evidence
18		-
19		-Mutations at the main hotspot and some less common hotspots lead to enhanced methylation by PRC2.[@yapSomaticMutationsEZH22011]
20		-A number of small molecule/pharmacologic inhibitors of EZH2 activity have been described.[@garapaty-raoIdentificationEZH2EZH12013; @knutsonSelectiveInhibitionEZH22014] At least one of these, tazemetostat, has shown benefit in FL.[@morinTreatingLymphomaNow2021]
21		-Combination therapies including EZH2 inhibitors are also under exploration for DLBCL patients with mutant EZH2.[@scholzeCombinedEZH2Bcl22020]
22		-
23		-
24		-## Relevance tier by entity
25		-
26		-[[include:tables/table1_EZH2]]
27		-
28		-## Mutation incidence in large patient cohorts (GAMBL reanalysis)
29		-
30		-
31		-### DLBCL
32		-[[include:tables/DLBCL_EZH2.md]]
33		-
34		-### FL
35		-[[include:tables/FL_EZH2.md]]
36		-
37		-### BL
38		-[[include:tables/BL_EZH2.md]]
39		-
40		-
41		-## Mutation pattern and selective pressure estimates
42		-
43		-[[include:tables/dnds_EZH2.md]]
44		-
45		-## EZH2 Hotspots
46		-
47		-\| Chromosome \|Coordinate (hg19) \| ref>alt \| HGVSp \|
48		- \| :---:\| :---: \| :--: \| :---: \|
49		-\| chr7 \| 148508745 \| T>C \| N640S \|
50		-\|chr7\|148508740\|A>G\|F642L\|
51		-\| chr7 \| 148508728 \| A>T \| Y646N \|
52		-\| chr7 \| 148508728 \| A>G \| Y646H \|
53		-\| chr7 \| 148508727 \| T>G \| Y646S \|
54		-\| chr7 \| 148508727 \| T>C \| Y646C \|
55		-\| chr7 \| 148508727 \| T>A \| Y646F \|
56		-\|chr7\|148506466\|TG>GC\|A682G\|
57		-\|chr7\|148506467\|G>C\|A682G\|
58		-\|chr7\|148506437\|GC>AA\|A692L\|
59		-\|chr7\|148506437\|G>A\|A692V\|
60		-
61		-[[include:tables/browser_EZH2.md]]
62		-
63		-## Expression
64		-![](images/gene_expression/EZH2_by_pathology.svg)
65		-
66		-## Representative Mutations
67		-
68		-### BL
69		-
70		-![](primary/Love_EZH2.svg)
71		-Rating
72		-&starf; &starf; &starf; &starf; &starf;
73		-
74		-## All Mutations
75		-
76		-### BL
77		-
78		-[@loveGeneticLandscapeMutations2012]
79		-
80		-[1092](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Love/1092_reports.html)
81		-[671](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Love/671_reports.html)
82		-[672](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Love/672_reports.html)
83		-[675](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Love/675_reports.html)
84		-
85		-<!-- ORIGIN: morinSomaticMutationsAltering2010 -->
86		-<!-- BL: loveGeneticLandscapeMutations2012 -->
87		-<!-- FL: morinSomaticMutationsAltering2010a -->
88		-<!-- BL: loveGeneticLandscapeMutations2012 -->
89		-<!-- DLBCL: morinSomaticMutationsAltering2010 -->
90		-<!-- PMBL: mottokIntegrativeGenomicAnalysis2019b -->
91		-
92		-[[include:tables/mermaid_EZH2.md]]
93		-
94		-## References
95		-