Changes in 02fd9b3: Updated KLHL6 (markdown)

				KLHL6.md
			
          @@ -1,27 +1,28 @@

           # KLHL6

           ## Overview

          -KLHL6 mutations appear to be relatively common in DLBCL, FL and possibly BL.<sup>1</sup> KLHL6 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus.

          +KLHL6 mutations appear to be relatively common in DLBCL, FL and possibly BL.<sup>1</sup> KLHL6 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. KLHL6 mutations lead to the loss of its function as part of a cullin-RING ubiquitin ligase complex. 

          +KLHL6 is considered a tumor suppressor gene in DLBCL with mutations tending to disrupt its interaction with cullin3, leading to the loss of its ligase activity.<sup>2</sup> 

           ## Relevance tier by entity

           |Entity|Tier|Description                           |

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

          -|BL    |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous |

           |DLBCL |1-a | aSHM target and high-confidence DLBCL gene            |

           |FL    |1-a | aSHM target and high-confidence FL gene               |

          +|BL    |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous |

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

           |Entity|source               |frequency (%)|

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

          -|BL    |GAMBL genomes+capture|3.93         |

          -|BL    |Thomas cohort        |3.00         |

          -|BL    |Panea cohort         |6.90         |

           |DLBCL |GAMBL genomes        |5.35         |

           |DLBCL |Schmitz cohort       |9.15         |

           |DLBCL |Reddy cohort         |6.41         |

           |DLBCL |Chapuy cohort        |8.97         |

           |FL    |GAMBL genomes        |7.16         |

          +|BL    |GAMBL genomes+capture|3.93         |

          +|BL    |Thomas cohort        |3.00         |

          +|BL    |Panea cohort         |6.90         |

           ## Mutation pattern and selective pressure estimates

          @@ -37,9 +38,6 @@ KLHL6 mutations appear to be relatively common in DLBCL, FL and possibly BL.<sup

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

           |chr3    |183269360 |183274139|[TSS](https://genome.ucsc.edu/s/rdmorin/GAMBL%20hg19?position=chr3%3A183269360%2D183274139)|active_promoter-strong_enhancer|

          -> [!NOTE]

          -> First described in DLBCL in 2011 by [Morin RD](https://pubmed.ncbi.nlm.nih.gov/21796119). First described in FL in 2011 by [Morin RD](https://pubmed.ncbi.nlm.nih.gov/21796119)

          -

            ## KLHL6 Hotspots

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

          @@ -76,4 +74,5 @@ View all variants in GenomePaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/K

           ![image](images/proteinpaint/KLHL6.svg)

           ## References

          -1. *Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351. PMID: 21796119; PMCID: PMC3210554.*

          \ No newline at end of file

          +1. *Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351. PMID: 21796119; PMCID: PMC3210554.*

          +2. *Choi, J., Zhou, N., & Busino, L. (2019). KLHL6 is a tumor suppressor gene in diffuse large B-cell lymphoma. Cell Cycle, 18, 249 - 256. https://doi.org/10.1080/15384101.2019.1568765.*

          \ No newline at end of file

...	...	@@ -1,27 +1,28 @@
1	1	# KLHL6
2	2	## Overview
3		-KLHL6 mutations appear to be relatively common in DLBCL, FL and possibly BL.<sup>1</sup> KLHL6 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus.
	3	+KLHL6 mutations appear to be relatively common in DLBCL, FL and possibly BL.<sup>1</sup> KLHL6 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. KLHL6 mutations lead to the loss of its function as part of a cullin-RING ubiquitin ligase complex.
	4	+KLHL6 is considered a tumor suppressor gene in DLBCL with mutations tending to disrupt its interaction with cullin3, leading to the loss of its ligase activity.<sup>2</sup>
4	5
5	6	## Relevance tier by entity
6	7
7	8	\|Entity\|Tier\|Description \|
8	9	\|:------:\|:----:\|--------------------------------------\|
9		-\|BL \|2-a \| aSHM target; Although recurrent, the relevance of mutations in BL is tenuous \|
10	10	\|DLBCL \|1-a \| aSHM target and high-confidence DLBCL gene \|
11	11	\|FL \|1-a \| aSHM target and high-confidence FL gene \|
	12	+\|BL \|2-a \| aSHM target; Although recurrent, the relevance of mutations in BL is tenuous \|
12	13
13	14	## Mutation incidence in large patient cohorts (GAMBL reanalysis)
14	15
15	16	\|Entity\|source \|frequency (%)\|
16	17	\|:------:\|:---------------------:\|:-------------:\|
17		-\|BL \|GAMBL genomes+capture\|3.93 \|
18		-\|BL \|Thomas cohort \|3.00 \|
19		-\|BL \|Panea cohort \|6.90 \|
20	18	\|DLBCL \|GAMBL genomes \|5.35 \|
21	19	\|DLBCL \|Schmitz cohort \|9.15 \|
22	20	\|DLBCL \|Reddy cohort \|6.41 \|
23	21	\|DLBCL \|Chapuy cohort \|8.97 \|
24	22	\|FL \|GAMBL genomes \|7.16 \|
	23	+\|BL \|GAMBL genomes+capture\|3.93 \|
	24	+\|BL \|Thomas cohort \|3.00 \|
	25	+\|BL \|Panea cohort \|6.90 \|
25	26
26	27	## Mutation pattern and selective pressure estimates
27	28
...	...	@@ -37,9 +38,6 @@ KLHL6 mutations appear to be relatively common in DLBCL, FL and possibly BL.<sup
37	38	\|:--------:\|:----------:\|:---------:\|:-------------------------------------------------------------------------------------------:\|:-------------------------------:\|
38	39	\|chr3 \|183269360 \|183274139\|[TSS](https://genome.ucsc.edu/s/rdmorin/GAMBL%20hg19?position=chr3%3A183269360%2D183274139)\|active_promoter-strong_enhancer\|
39	40
40		-> [!NOTE]
41		-> First described in DLBCL in 2011 by [Morin RD](https://pubmed.ncbi.nlm.nih.gov/21796119). First described in FL in 2011 by [Morin RD](https://pubmed.ncbi.nlm.nih.gov/21796119)
42		-
43	41	## KLHL6 Hotspots
44	42
45	43	\| Chromosome \|Coordinate (hg19) \| ref>alt \| HGVSp \|
...	...	@@ -76,4 +74,5 @@ View all variants in GenomePaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/K
76	74	![image](images/proteinpaint/KLHL6.svg)
77	75
78	76	## References
79		-1. Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351. PMID: 21796119; PMCID: PMC3210554.
...	...	\ No newline at end of file
	0	+1. Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351. PMID: 21796119; PMCID: PMC3210554.
	1	+2. Choi, J., Zhou, N., & Busino, L. (2019). KLHL6 is a tumor suppressor gene in diffuse large B-cell lymphoma. Cell Cycle, 18, 249 - 256. https://doi.org/10.1080/15384101.2019.1568765.
...	...	\ No newline at end of file