P 14: RNA fusions involving CD28 contribute to mutations-induced TCR signaling activation in peripheral T-cell lymphomas of TFH derivation
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ID Serval
serval:BIB_83449E0A95A7
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
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Poster: résume de manière illustrée et sur une page unique les résultats d'un projet de recherche. Les résumés de poster doivent être entrés sous "Abstract" et non "Poster".
Collection
Publications
Institution
Titre
P 14: RNA fusions involving CD28 contribute to mutations-induced TCR signaling activation in peripheral T-cell lymphomas of TFH derivation
Titre de la conférence
Swiss Pathology Days
Adresse
Thun, Switzerland, November 10-12, 2017
ISSN
0172-8113
1432-1963
1432-1963
ISSN-L
1432-1963
Statut éditorial
Publié
Date de publication
20/10/2017
Volume
38
Numéro
6
Série
Der Pathologe
Pages
578-579
Langue
anglais
Résumé
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%)
Création de la notice
13/11/2017 14:47
Dernière modification de la notice
20/08/2019 15:43
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