MCL1 - morinlab/LLMPP GitHub Wiki

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MCL1

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.1,2 Recurrent chromosomal gains and amplifications of the MCL1 locus occur are frequent in ABC-DLBCLs.1
MCL1 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus.

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%%
timeline
    title Publication timing
      2017-10-10 : Reddy : DLBCL
      2019-09-26 : Panea : BL
      2021-07-15 : Duns : PMBL
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Relevance tier by entity

Entity Tier Description
PMBL 2 relevance in PMBL/cHL/GZL not firmly established[@dunsCharacterizationDLBCLPMBL2021b]
BL 2-a aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@paneaWholeGenomeLandscape2019]
DLBCL 1-a 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

Entity aSHM Significant selection dN/dS (missense) dN/dS (nonsense)
BL Yes No 5.101 0.000
DLBCL Yes No 0.427 2.401
FL Yes No 0.000 0.000

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr1 150550814 150552135 intron NA

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

MCL1 Expression

Representative Mutations

DLBCL

Rating ★ ★ ☆ ☆ ☆

Rating ★ ★ ★ ☆ ☆

All Mutations

Reddy_2074T Reddy_2114T Reddy_2124T Reddy_2148T Reddy_2150T Reddy_2153T Reddy_2156T Reddy_2215T Reddy_2233T Reddy_2476T Reddy_2478T Reddy_2482T Reddy_2525T Reddy_2540T Reddy_2542T Reddy_2554T Reddy_2649T Reddy_2706T Reddy_2713T Reddy_2727T Reddy_2819T Reddy_2832T Reddy_2874T Reddy_2948T Reddy_2952T Reddy_3385T Reddy_3454T Reddy_3468T Reddy_3471T Reddy_3476T Reddy_3527T Reddy_3547T Reddy_3593T Reddy_3602T Reddy_3622T Reddy_3664T Reddy_3667T Reddy_3766T Reddy_3777T Reddy_3782T Reddy_3811T Reddy_3817T Reddy_3825T Reddy_3829T Reddy_3837T Reddy_3927T Reddy_3952T Reddy_3965T Reddy_3966T Reddy_3984T Reddy_689T Reddy_830T

References

38(2):136–148. PMID: 33684939*

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