P 14: RNA fusions involving CD28 contribute to mutations-induced TCR signaling activation in peripheral T-cell lymphomas of TFH derivation
Details
Serval ID
serval:BIB_83449E0A95A7
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Poster: Summary – with images – on one page of the results of a researche project. The summaries of the poster must be entered in "Abstract" and not "Poster".
Collection
Publications
Institution
Title
P 14: RNA fusions involving CD28 contribute to mutations-induced TCR signaling activation in peripheral T-cell lymphomas of TFH derivation
Title of the conference
Swiss Pathology Days
Address
Thun, Switzerland, November 10-12, 2017
ISSN
0172-8113
1432-1963
1432-1963
ISSN-L
1432-1963
Publication state
Published
Issued date
20/10/2017
Volume
38
Number
6
Series
Der Pathologe
Pages
578-579
Language
english
Abstract
Background: Recently, RNA sequencing analysis revealed rare (2.5–5%)
fusions of CD28 to CTLA4 or ICOS in AITL (Angioimmunoblastic T-cell
Lymphoma), CTCL (Cutaneous T-Cell Lymphoma) or ATLL (Adult T-cell
Leukaemia/Lymphoma). However, a high frequency of CTLA4(ex3)_
CD28(ex4) fusion was found (38%) in a large series of AITL, PTCL-NOS
and ENKTCL (Extranodal Natural Killer/T-cell Lymphoma) FFPE samples.
We screened the described CD28 fusions by RT-PCR in 276 frozen
PTCL samples (113 AITL, 24 T-follicular helper-derived (TFH) PTCL, 4
Follicular (F-) PTCL, 63 PTCL-NOS, 26 CTCL, 18 ENKTCL, 10 EATL
(Enteropathy Associated T-cell Lymphoma), 9 ALK-negative ALCL (Anaplasic
Large Cell Lymphoma), 6 ATLL and 3 HSTL (Hepatosplenic T-cell
Lymphoma)) from the Tenomic biobank.
Methods: Samples were shared equally between Lausanne and Creteil laboratories
for molecular screening with all positive cases and 20% of negative
cases crossvalidated in both.
Results: Overall, 15CD28 fusions were detected in 13/276 cases (9 TFH-derived
PTCL, 2 PTCL-NOS, 1 ATLL and 1 CTCL). The most common rearrangements
were ICOS(ex1)_CD28(ex2) (11/15 fusions) and CTLA4(ex3)_
CD28(ex4) (3/15 fusions) while CTLA4(ex2)_CD28(ex4) was identified in
a single CTCL. CD28 fusions were found in 9/141 TFHderived PTCLs
(AITL and others), of these 8/9 cases harbored ICOS(ex1)_CD28(ex2) fusion
including one with an additional CTLA4(ex3)_CD28(ex4) fusion. In
a subset of 100 TFH-derived PTCLs also explored by targeting deep sequencing,
CD28 alterations (mutations and fusions) in isolation did not
impact OS or PFS, but alterations in one or several of a larger panel of
TCR-related led to shorter OS (p=0.06) and significantly shorter PFS.
Analysis of gene expression signatures by GSEA (gene set enrichment analysis) indicated that CD28 alterations contributed to mutations-induced
TCR signalling activation.
Conclusions: Rearrangements fusing CD28 and CTLA4 or ICOS are rare
in PTCL (4.7%), relatively more frequent in TFHderived entities (6.4%)
and most commonly represented by ICOS(ex1)_CD28(ex2) fusion (73%)
fusions of CD28 to CTLA4 or ICOS in AITL (Angioimmunoblastic T-cell
Lymphoma), CTCL (Cutaneous T-Cell Lymphoma) or ATLL (Adult T-cell
Leukaemia/Lymphoma). However, a high frequency of CTLA4(ex3)_
CD28(ex4) fusion was found (38%) in a large series of AITL, PTCL-NOS
and ENKTCL (Extranodal Natural Killer/T-cell Lymphoma) FFPE samples.
We screened the described CD28 fusions by RT-PCR in 276 frozen
PTCL samples (113 AITL, 24 T-follicular helper-derived (TFH) PTCL, 4
Follicular (F-) PTCL, 63 PTCL-NOS, 26 CTCL, 18 ENKTCL, 10 EATL
(Enteropathy Associated T-cell Lymphoma), 9 ALK-negative ALCL (Anaplasic
Large Cell Lymphoma), 6 ATLL and 3 HSTL (Hepatosplenic T-cell
Lymphoma)) from the Tenomic biobank.
Methods: Samples were shared equally between Lausanne and Creteil laboratories
for molecular screening with all positive cases and 20% of negative
cases crossvalidated in both.
Results: Overall, 15CD28 fusions were detected in 13/276 cases (9 TFH-derived
PTCL, 2 PTCL-NOS, 1 ATLL and 1 CTCL). The most common rearrangements
were ICOS(ex1)_CD28(ex2) (11/15 fusions) and CTLA4(ex3)_
CD28(ex4) (3/15 fusions) while CTLA4(ex2)_CD28(ex4) was identified in
a single CTCL. CD28 fusions were found in 9/141 TFHderived PTCLs
(AITL and others), of these 8/9 cases harbored ICOS(ex1)_CD28(ex2) fusion
including one with an additional CTLA4(ex3)_CD28(ex4) fusion. In
a subset of 100 TFH-derived PTCLs also explored by targeting deep sequencing,
CD28 alterations (mutations and fusions) in isolation did not
impact OS or PFS, but alterations in one or several of a larger panel of
TCR-related led to shorter OS (p=0.06) and significantly shorter PFS.
Analysis of gene expression signatures by GSEA (gene set enrichment analysis) indicated that CD28 alterations contributed to mutations-induced
TCR signalling activation.
Conclusions: Rearrangements fusing CD28 and CTLA4 or ICOS are rare
in PTCL (4.7%), relatively more frequent in TFHderived entities (6.4%)
and most commonly represented by ICOS(ex1)_CD28(ex2) fusion (73%)
Create date
13/11/2017 13:47
Last modification date
20/08/2019 14:43
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