MYC

Overview

MYC 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 1992-12-01 : Johnston : BL 2001-07-19 : Pasqualucci : DLBCL 2017-07-27 : Jallades : MZL 2021-07-15 : Duns : PMBL

Relevance tier by entity

Entity	Tier	Description
	2	relevance in PMBL/cHL/GZL not firmly established¹
	2	relevance in MZL not firmly established²
	1-a	aSHM target and high-confidence BL gene³
	1-a	aSHM target and high-confidence DLBCL gene⁴
	2-a	aSHM target; Although recurrent, the relevance of mutations in FL is tenuous

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	61.89
BL	Thomas cohort	60.20
BL	Panea cohort	49.50
DLBCL	GAMBL genomes	10.90
DLBCL	Schmitz cohort	5.32
DLBCL	Reddy cohort	6.21
DLBCL	Chapuy cohort	6.41
FL	GAMBL genomes	0.92

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	Yes	7.754	3.964
DLBCL	Yes	Yes	2.850	2.582
FL	Yes	No	4.998	0.000

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr8	128748352	128749427	TSS	active_promoter

MYC Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr8	128750677	C>A	P72T
chr8	128750677	C>G	P72A
chr8	128750677	C>T	P72S
chr8	128750677	CC>TT	P72F
chr8	128750678	C>G	P72R
chr8	128750678	C>T	P72L
chr8	128750680	A>G	T73A
chr8	128750681	C>A	T73N
chr8	128750681	C>T	T73I
chr8	128750681	CC>AT	T73N
chr8	128750681	CC>GT	T73S
chr8	128750681	CC>TA	T73I
chr8	128750681	CC>TG	T73M
chr8	128750681	CC>TT	T73I
chr8	128750683	C>G	P74A
chr8	128750683	C>T	P74S
chr8	128750684	C>T	P74L
chr8	128750686	C>A	P75T
chr8	128750686	C>G	P75A
chr8	128750686	C>T	P75S
chr8	128750686	CC>TT	P75F
chr8	128750687	C>A	P75H
chr8	128750687	C>G	P75R
chr8	128750692	T>C	S77P
chr8	128750692	T>G	S77A
chr8	128750693	C>G	S77C
chr8	128750695	C>T	P78S
chr8	128750696	C>G	P78R

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

MYC Expression

References

Duns G, Viganò E, Ennishi D, Sarkozy C, Hung SS, Chavez E, Takata K, Rushton C, Jiang A, Ben-Neriah S, Woolcock BW, Slack GW, Hsi ED, Craig JW, Hilton LK, Shah SP, Farinha P, Mottok A, Gascoyne RD, Morin RD, Savage KJ, Scott DW, Steidl C. Characterization of DLBCL with a PMBL gene expression signature. Blood. 2021 Jul 15;138(2):136–148.

Jallades L, Baseggio L, Sujobert P, Huet S, Chabane K, Callet-Bauchu E, Verney A, Hayette S, Desvignes JP, Salgado D, Levy N, Béroud C, Felman P, Berger F, Magaud JP, Genestier L, Salles G, Traverse-Glehen A. Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma. Haematologica. 2017 Oct;102(10):1758–1766. PMCID: PMC5622860

Johnston JM, Carroll WL. C-myc hypermutation in Burkitt’s lymphoma. Leuk Lymphoma. 1992 Dec;8(6):431–439.

Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Küppers R, Dalla-Favera R. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature. 2001 Jul 19;412(6844):341–346.