hubschmannMutationalMechanismsShaping2021

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title: '' bibliography: 'morinlab.bib'

@hubschmannMutationalMechanismsShaping2021

Study Overview

In their 2021 study published in Leukemia, Hübschmann et al. conducted a comprehensive analysis of 181 germinal center-derived B-cell lymphomas (gcBCLs) using whole-genome and transcriptome sequencing. The research aimed to elucidate the mutational mechanisms influencing both coding and noncoding regions of the genome in these lymphomas.

Key Findings

Mutational Signatures

• The study identified distinct mutational signatures associated with somatic hypermutation (SHM) and class-switch recombination (CSR).
• Both SHM and CSR were found to contribute to off-target mutations in non-immunoglobulin (non-IG) genes, suggesting a broader impact on genomic integrity.

Noncoding Regions

• Mutations were prevalent in noncoding regions, including promoters and enhancers, indicating potential regulatory disruptions.
• These noncoding mutations may influence gene expression and contribute to lymphomagenesis.

Pathway Alterations

• Recurrent mutations were observed in pathways related to B-cell development and function, such as the NF-κB and JAK-STAT signaling pathways.
• These alterations underscore the role of specific signaling cascades in the pathogenesis of gcBCLs.

Clinical Implications

• The findings highlight the significance of both coding and noncoding mutations in the development of gcBCLs.
• Understanding these mutational mechanisms may inform targeted therapeutic strategies and improve diagnostic precision.

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Conclusion

Hübschmann et al.'s study provides valuable insights into the mutational processes shaping the genomes of germinal center-derived B-cell lymphomas. By revealing the contributions of SHM and CSR to off-target mutations and emphasizing the importance of noncoding regions, this research advances our understanding of lymphoma biology and potential avenues for treatment.

Summary of novel genes

Entity	Tier 1 genes	Tier 2 genes	Tier 3 genes
FL	2	16	0
DLBCL	4	20	3

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sankey-beta
This study, New Tier 1, 4
New Tier 1, DLBCL Tier 1, 4
This study, New Tier 2, 20
New Tier 2, DLBCL Tier 2, 20
This study, New Tier 3, 3
New Tier 3, DLBCL Tier 3, 3
All other DLBCL studies, DLBCL Tier 1, 121
All other DLBCL studies, DLBCL Tier 2, 190
All other DLBCL studies, DLBCL Tier 3, 384

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Novel genes reported in this study

Tier 1

New gene	FL tier	DLBCL tier	Average variant quality	QC outcome
ACTG1	2	1
EEF1A1	1	1
HLA-DMB		1
MEF2C	2	1
VMA21	1

Tier 2

New gene	FL tier	DLBCL tier	Average variant quality	QC outcome
ADAMTS1		2	★ ★ ★ ☆ ☆	PASS
ANKRD12		2	★ ★ ★ ☆ ☆	PASS
ATP6V1A	2
CADPS2		2	★ ★ ★ ★ ☆	PASS
CDC42BPB	2
CNOT2		2	★ ★ ★ ★ ☆	PASS
CPNE8	2
DHX15	2
DHX16		2	★ ★ ★ ★ ☆	PASS
DNM2		2	★ ★ ★ ☆ ☆	PASS
FZR1	2
IKBKE		2	★ ★ ★ ★ ☆	PASS
IRF1		2	★ ★ ★ ☆ ☆	PASS
JUP	2
LAPTM5	2	2	★ ★ ★ ★ ☆	PASS
LRP12		2	★ ★ ★ ☆ ☆	PASS
MGEA5	2
MYCBP2	2
PDS5B	2	2	★ ★ ★ ★ ☆	PASS
PNPO		2	★ ★ ★ ☆ ☆	PASS
PPP4C	2
PRKDC	2	2
RAC2		2	★ ★ ★ ☆ ☆	PASS
RBM6	2
SIAH2		2	★ ★ ★ ☆ ☆	PASS
SLC34A2		2	★ ★ ★ ☆ ☆	PASS
TPP1	2
TRAF6		2	★ ★ ★ ☆ ☆	PASS
UNC5B		2	★ ★ ★ ☆ ☆	PASS
WNK1		2	★ ★ ★ ☆ ☆	PASS
ZNF217		2	★ ★ ★ ☆ ☆	PASS

Tier 3

New gene	FL tier	DLBCL tier	Average variant quality	QC outcome
GAK		3	★ ★ ☆ ☆ ☆	FAIL
HLA-DQA1		3	★ ★ ☆ ☆ ☆	FAIL
NR2F2		3	★ ★ ☆ ☆ ☆	FAIL

Details