Table of Contents

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.

Experimental Evidence

Driver mutations affecting this gene in DLBCL/FL/BL have been experimentally demonstrated to cause a gain of function (GOF).1

Relevance tier by entity

Entity Tier Description
BL 1 High-confidence BL gene
DLBCL 1 High-confidence DLBCL gene
FL 1 High-confidence FL gene
MZL 2 Role of MYC mutations in MZL requires confirmation
PMBL 2 Role of MYC mutations in PMBL requires confirmation

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 69 0.0634 [0.0489,0.0778]
DLBCL GAMBL with Reddy 2,088 131 0.0627 [0.0523,0.0731]
DLBCL BC 231 13 0.0563 [0.0266,0.086]
DLBCL Dana-Farber 303 20 0.0660 [0.038,0.094]
DLBCL NCI 470 25 0.0532 [0.0329,0.0735]
DLBCL Reddy 999 62 0.0621 [0.0471,0.077]
DLBCL DLBCL_ICGC 85 11 0.1294 [0.0581,0.2008]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 6 0.0093 [0.0019,0.0168]
FL GAMBL with Crouch 1,189 15 0.0126 [0.0063,0.019]
FL BC 379 3 0.0079 [0,0.0168]
FL Kalmbach 164 2 0.0122 [0,0.029]
FL Crouch 547 9 0.0165 [0.0058,0.0271]
FL FL_ICGC 99 1 0.0101 [0,0.0298]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 197 0.6390 [0.5856,0.6924]
BL GAMBL without ICGC/Zhou 320 202 0.6332 [0.5806,0.6858]
BL GAMBL with Panea 410 254 0.6216 [0.5748,0.6683]
BL BLGSP 219 145 0.6621 [0.5995,0.7247]
BL Zhou/ICGC 90 52 0.5778 [0.4757,0.6798]
BL Panea 101 57 0.5644 [0.4677,0.6611]

Mutation pattern and selective pressure estimates

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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

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Expression

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References

1.
Freie B, Carroll PA, Varnum-Finney BJ, Ramsey EL, Ramani V, Bernstein I, Eisenman RN. A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies. Genes Dev. 2024 Apr 17;38(5-6):253–272. PMCID: PMC11065175
2.
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.
3.
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
4.
Johnston JM, Carroll WL. C-myc hypermutation in Burkitt’s lymphoma. Leuk Lymphoma. 1992 Dec;8(6):431–439.
5.
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.

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