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result(s) for
"Prahladan, Mahesh Panatt"
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Non-IG::MYC in diffuse large B-cell lymphoma confers variable genomic configurations and MYC transactivation potential
by
Tooze, Reuben
,
Chen, Zi
,
Makker, Jasmine
in
14/32
,
631/67/68
,
692/699/1541/1990/291/1621/1915
2024
MYC
translocation occurs in 8–14% of diffuse large B-cell lymphoma (DLBCL), and may concur with
BCL2
and/or
BCL6
translocation, known as double-hit (DH) or triple-hit (TH). DLBCL-
MYC
/
BCL2
-DH/TH are largely germinal centre B-cell like subtype, but show variable clinical outcome, with
IG
::
MYC
fusion significantly associated with inferior survival. While DLBCL-
MYC
/
BCL6
-DH are variable in their cell-of-origin subtypes and clinical outcome. Intriguingly, only 40-50% of DLBCL with
MYC
translocation show high MYC protein expression (>70%). We studied 186 DLBCLs with
MYC
translocation including 32
MYC/BCL2/BCL6
-TH
, 75 MYC/BCL2
-DH and 26
MYC/BCL6
-DH. FISH revealed a
MYC
/
BCL6
fusion in 59% of DLBCL-
MYC/BCL2/BCL6
-TH and 27% of DLBCL-
MYC
/
BCL6
-DH. Targeted NGS showed a similar mutation profile and LymphGen genetic subtype between DLBCL-
MYC/BCL2/BCL6
-TH and DLBCL-
MYC/BCL2
-DH, but variable LymphGen subtypes among DLBCL-
MYC
/
BCL6
-DH. MYC protein expression is uniformly high in DLBCL with
IG::MYC
, but variable in those with non-
IG::MYC
including
MYC
/
BCL6
-fusion. Translocation breakpoint analyses of 8 cases by TLC-based NGS showed no obvious genomic configuration that enables
MYC
transactivation in 3 of the 4 cases with non-
IG:
:
MYC
, while a typical promoter substitution or
IGH
super enhancer juxtaposition in the remaining cases. The findings potentially explain variable MYC expression in DLBCL with
MYC
translocation, and also bear practical implications in its routine assessment.
Journal Article