loveGeneticLandscapeMutations2012 - morinlab/LLMPP GitHub Wiki

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@loveGeneticLandscapeMutations2012

Summary

The 2012 study provided foundational insights into the genetic landscape of Burkitt lymphoma (BL), describing recurrent mutations in genes such as MYC, ID3, ARID1A, SMARCA4, and TP53. Subsequent research has both validated and expanded upon these findings. Although this study identified some genes that are commonly mutated in BL. Some of its novel findings are of questionable significance in BL.

Reproduced Findings

  • ID3 Mutations: The initial identification of ID3 mutations in approximately one-third of BL cases has been consistently corroborated. These mutations, particularly affecting the helix-loop-helix domain, are recognized as a hallmark of BL and are rare in other lymphomas.
  • ARID1A and SMARCA4 Mutations: Mutations in ARID1A and SMARCA4, components of the SWI/SNF chromatin-remodeling complex, have been confirmed in BL. These mutations are often mutually exclusive, suggesting that alteration in one is sufficient to disrupt the complex's function.
  • TP53 Mutations: Alterations in TP53 have been consistently observed in BL, underscoring its role in the disease's pathogenesis.

Expanded Insights

  • GNA13 Mutations: The initial study noted mutations in GNA13. Further research has highlighted its role in BL, particularly in germinal center B cell–derived lymphomas.
  • Additional Mutations: Subsequent studies have identified mutations in genes such as TCF3, CCND3, and DDX3X, which were not prominently featured in the 2012 study. These findings have enriched the understanding of BL's genetic complexity.

Less Reproduced Findings

  • CCT6B, SALL3, FTCD, and PC Mutations: The study reported mutations in a large number of genes including CCT6B, SALL3, FTCD, and PC. However, these findings have not been consistently replicated in subsequent research, suggesting they may be less central to BL's pathogenesis or represent less common alterations. Most of the genes from this study are now in Tier 3.

Summary of novel genes

Entity Tier 1 genes Tier 2 genes Tier 3 genes
BL 5 7 48 
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This study, New Tier 1, 5
New Tier 1, BL Tier 1, 5
This study, New Tier 2, 7
New Tier 2, BL Tier 2, 7
This study, New Tier 3, 48
New Tier 3, BL Tier 3, 48
All other BL studies, BL Tier 1, 27
All other BL studies, BL Tier 2, 65
All other BL studies, BL Tier 3, 22
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Novel genes reported in this study

Tier 1

New gene BL tier Average variant quality QC outcome
ARID1A 1
BCL6 1 β˜… β˜… β˜… β˜… β˜† PASS
CREBBP 1 β˜… β˜… β˜… β˜… β˜† PASS
GNA13 1
PTEN 1

Tier 2

New gene BL tier Average variant quality QC outcome
CARD4 2 β˜… β˜… β˜… β˜… β˜† PASS
CDC73 2 β˜… β˜… β˜… β˜† β˜† PASS
EZH2 2 β˜… β˜… β˜… β˜… β˜… PASS
GGTLA4 2 β˜… β˜… β˜… β˜… β˜† PASS
NBEAL1 2 β˜… β˜… β˜… β˜… β˜† PASS
P2RY2 2 β˜… β˜… β˜… β˜… β˜† PASS
RANBP6 2 β˜… β˜… β˜… β˜… β˜… PASS

Tier 3

New gene BL tier Average variant quality QC outcome
ACAD9 3 β˜… β˜† β˜† β˜† β˜† FAIL
ACE 3 β˜… β˜† β˜† β˜† β˜† FAIL
ATP2C2 3 β˜… β˜… β˜† β˜† β˜† FAIL
BRAF 3 β˜… β˜† β˜† β˜† β˜† FAIL
BRD4 3 β˜… β˜† β˜† β˜† β˜† FAIL
BTG2 3 β˜… β˜† β˜† β˜† β˜† FAIL
C6orf27 3 Germline FAIL
CAD 3 β˜… β˜† β˜† β˜† β˜† FAIL
CCT6B 3 Germline FAIL
CDH17 3 β˜… β˜† β˜† β˜† β˜† FAIL
COL4A2 3 β˜… β˜† β˜† β˜† β˜† FAIL
CYB5D1 3 β˜… β˜… β˜† β˜† β˜† FAIL
CYP4F22 3 β˜… β˜† β˜† β˜† β˜† FAIL
DLGAP1 3 β˜… β˜† β˜† β˜† β˜† FAIL
DTX1 3 β˜… β˜† β˜† β˜† β˜† FAIL
EIF2C4 3 β˜… β˜† β˜† β˜† β˜† FAIL
EML2 3 β˜… β˜† β˜† β˜† β˜† FAIL
ENTPD3 3 β˜… β˜… β˜† β˜† β˜† FAIL
EPHB2 3 β˜… β˜… β˜† β˜† β˜† FAIL
FAM129B 3 β˜… β˜… β˜† β˜† β˜† FAIL
FGFR3 3 β˜… β˜† β˜† β˜† β˜† FAIL
FTCD 3 Germline FAIL
GRIK5 3 β˜… β˜† β˜† β˜† β˜† FAIL
ICK 3 β˜… β˜† β˜† β˜† β˜† FAIL
ITPR3 3 β˜… β˜† β˜† β˜† β˜† FAIL
KIFC3 3 β˜… β˜† β˜† β˜† β˜† FAIL
MAP3K6 3 β˜… β˜† β˜† β˜† β˜† FAIL
MYH10 3 β˜… β˜† β˜† β˜† β˜† FAIL
NOTCH1 3 β˜… β˜† β˜† β˜† β˜† FAIL
NRXN2 3 β˜… β˜† β˜† β˜† β˜† FAIL
PC 3 β˜… β˜† β˜† β˜† β˜† FAIL
POLRMT 3 β˜… β˜† β˜† β˜† β˜† FAIL
POR 3 β˜… β˜† β˜† β˜† β˜† FAIL
PRSS22 3 β˜… β˜† β˜† β˜† β˜† FAIL
PTPRN 3 β˜… β˜† β˜† β˜† β˜† FAIL
RBP3 3 β˜… β˜† β˜† β˜† β˜† FAIL
RET 3 β˜… β˜† β˜† β˜† β˜† FAIL
SALL3 3 β˜… β˜… β˜† β˜† β˜† FAIL
SAPS2 3 β˜… β˜† β˜† β˜† β˜† FAIL
SBF1 3 β˜… β˜… β˜† β˜† β˜† FAIL
SF3B1 3 β˜… β˜… β˜… β˜… β˜† FAIL
SHANK1 3 β˜… β˜† β˜† β˜† β˜† FAIL
SLC29A2 3 β˜… β˜† β˜† β˜† β˜† FAIL
SYNGAP1 3 β˜… β˜† β˜† β˜† β˜† FAIL
TBC1D9B 3 β˜… β˜† β˜† β˜† β˜† FAIL
TIGD6 3 β˜… β˜† β˜† β˜† β˜† FAIL
TPST2 3 β˜† β˜† β˜† β˜† β˜† FAIL
ZNF229 3 Germline FAIL

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