PIM1 - morinlab/LLMPP GitHub Wiki

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PIM1

Overview

PIM1 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
      2001-07-19 : Pasqualucci : DLBCL
      2021-07-15 : Duns : PMBL
      2022-07-06 : Burkhardt : BL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene[@dunsCharacterizationDLBCLPMBL2021b]
	2-a	aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@burkhardtClinicalRelevanceMolecular2022b]
	1-a	aSHM target and high-confidence DLBCL gene [@pasqualucciHypermutationMultipleProtooncogenes2001a]
	1-a	aSHM target and high-confidence FL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	2.31
BL	Thomas cohort	NA
BL	Panea cohort	NA
DLBCL	GAMBL genomes	20.27
DLBCL	Schmitz cohort	27.66
DLBCL	Reddy cohort	19.12
DLBCL	Chapuy cohort	23.93
FL	GAMBL genomes	9.24

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	No	6.021	0.000
DLBCL	Yes	Yes	2.096	2.418
FL	Yes	No	4.214	0.000

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr6	37138104	37139804	TSS	active_promoter

PIM1 Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr6	37138406	G>A	D19N
chr6	37138419	C>G	T23S
chr6	37138423	G>C	K24N
chr6	37138423	G>T	K24N
chr6	37138427	G>A	A26T
chr6	37138430	C>A	P27T
chr6	37138549	G>A	G28D
chr6	37138554	G>A	E30K
chr6	37138560	G>A	E32K
chr6	37138563	C>T	P33S
chr6	37138566	C>G	L34V
chr6	37138573	C>T	S36L
chr6	37138576	AG>TA	Q37L
chr6	37138577	G>C	Q37H
chr6	37138583	G>C	Q39H
chr6	37138593	C>G	L43V
chr6	37138596	C>A	L44M
chr6	37138596	C>G	L44V
chr6	37138603	GCG>-	G48del
chr6	37138604	C>A	S46R

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38