--- bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true --- [[_TOC_]] ## Overview MCL1 (Myeloid Cell Leukemia 1) is a member of the BCL2 family of proteins that play a critical role in inhibiting apoptosis. It is frequently overexpressed and sometimes mutated in DLBCL.[@dunsCharacterizationDLBCLPMBL2021; @paneaWholeGenomeLandscape2019] Recurrent chromosomal gains and amplifications of the MCL1 locus occur are frequent in ABC-DLBCLs.[@dunsCharacterizationDLBCLPMBL2021] MCL1 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. ## Relevance tier by entity |Entity|Tier|Description | |:------:|:----:|--------------------------------------| |![PMBL](images/icons/PMBL_tier2.png)|2|relevance in PMBL/cHL/GZL not firmly established[@dunsCharacterizationDLBCLPMBL2021]| |![BL](images/icons/BL_tier2.png) |2 | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@paneaWholeGenomeLandscape2019]| |![DLBCL](images/icons/DLBCL_tier1.png) |1 | aSHM target and high-confidence DLBCL gene [@reddyGeneticFunctionalDrivers2017]| ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |Entity|source |frequency (%)| |:------:|:---------------------:|:-------------:| |BL |GAMBL genomes+capture|1.85 | |BL |Thomas cohort |2.10 | |BL |Panea cohort |2.00 | |DLBCL |GAMBL genomes |2.49 | |DLBCL |Schmitz cohort |3.62 | |DLBCL |Reddy cohort |4.70 | |DLBCL |Chapuy cohort |3.42 | ## Mutation pattern and selective pressure estimates [[include:dnds_MCL1.md]] ## aSHM regions |chr_name|hg19_start|hg19_end |region |regulatory_comment| |:--------:|:----------:|:---------:|:----------------------------------------------------------------------------------------------:|:------------------:| |chr1 |150550814 |150552135|[intron](https://genome.ucsc.edu/s/rdmorin/GAMBL%20hg19?position=chr1%3A150550814%2D150552135)|NA | [[include:browser_MCL1.md]] ## Expression ![](images/gene_expression/MCL1_by_pathology.svg) ## Representative Mutations ### DLBCL ![](primary/Reddy_MCL1_2.svg) **Rating** ★ ★ ☆ ☆ ☆ ![](primary/Reddy_MCL1_3.svg) **Rating** ★ ★ ★ ☆ ☆ ## All Mutations [Reddy_2074T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2074T.html) [Reddy_2114T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2114T.html) [Reddy_2124T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2124T.html) [Reddy_2148T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2148T.html) [Reddy_2150T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2150T.html) [Reddy_2153T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2153T.html) [Reddy_2156T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2156T.html) [Reddy_2215T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2215T.html) [Reddy_2233T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2233T.html) [Reddy_2476T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2476T.html) [Reddy_2478T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2478T.html) [Reddy_2482T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2482T.html) [Reddy_2525T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2525T.html) [Reddy_2540T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2540T.html) [Reddy_2542T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2542T.html) [Reddy_2554T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2554T.html) [Reddy_2649T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2649T.html) [Reddy_2706T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2706T.html) [Reddy_2713T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2713T.html) [Reddy_2727T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2727T.html) [Reddy_2819T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2819T.html) [Reddy_2832T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2832T.html) [Reddy_2874T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2874T.html) [Reddy_2948T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2948T.html) [Reddy_2952T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_2952T.html) [Reddy_3385T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3385T.html) [Reddy_3454T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3454T.html) [Reddy_3468T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3468T.html) [Reddy_3471T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3471T.html) [Reddy_3476T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3476T.html) [Reddy_3527T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3527T.html) [Reddy_3547T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3547T.html) [Reddy_3593T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3593T.html) [Reddy_3602T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3602T.html) [Reddy_3622T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3622T.html) [Reddy_3664T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3664T.html) [Reddy_3667T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3667T.html) [Reddy_3766T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3766T.html) [Reddy_3777T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3777T.html) [Reddy_3782T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3782T.html) [Reddy_3811T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3811T.html) [Reddy_3817T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3817T.html) [Reddy_3825T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3825T.html) [Reddy_3829T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3829T.html) [Reddy_3837T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3837T.html) [Reddy_3927T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3927T.html) [Reddy_3952T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3952T.html) [Reddy_3965T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3965T.html) [Reddy_3966T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3966T.html) [Reddy_3984T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_3984T.html) [Reddy_689T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_689T.html) [Reddy_830T](https://www.bcgsc.ca/downloads/morinlab/GAMBL/Reddy/igv_reports/Reddy_830T.html) [[include:mermaid_MCL1.md]] ## References