Defining signatures of peripheral T-cell lymphoma with a targeted 20-marker gene expression profiling assay

Drieux, Fanny; Ruminy, Philippe; Abdel-Sater, Ahmad; Lemonnier, François; Viailly, Pierre‐Julien; Fataccioli, Virginie; Marchand, Vinciane; Bisig, Bettina; Letourneau, Audrey; Parrens, Marie; Bossard, Céline; Bruneau, Julie; Dobay, Pamela; Veresezan, Liana; Dupuy, Aurélie; Pujals, Anaïs; Robe, Cyrielle; Sako, Nouhoum; Copie‐Bergman, Christiane; Delfau‐Larue, Marie‐Hélène; Picquenot, Jean‐Michel; Tilly, Hervé; Delarue, Richard; Jardin, Fabrice; Leval, Laurence de; Gaulard, Philippe

doi:10.3324/haematol.2019.226647

Cited by 26 publications

(29 citation statements)

References 31 publications

(50 reference statements)

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“…These series of cases show that the expression of GATA3/TBX21 is not associated with changes in survival probability, in contrast with the findings of Iqbal and coworkers 9,23,25 . Our findings are consistent with those of Drieux's group 7 , although both studies featured relatively small numbers of cases with a diagnosis of PTCL-NOS.…”

Section: Discussionsupporting

confidence: 92%

“…Differential diagnosis of these three main subtypes of PTCL involves a combination of clinical, histological and immunohistochemical markers, but frequently requires more specific markers, and has relatively low reproducibility 6 . Several projects have since evaluated whether gene expression analysis could improve diagnostic accuracy by delineating specific T-cell lymphoma classes or by identifying more precise prognostic models 2,3,[7][8][9][10] . Nevertheless, the need for reliable diagnostic and prognostic markers in PTCL/AITL remains partially unmet.…”

Section: Introductionmentioning

confidence: 99%

“… 6 Several projects have since evaluated whether gene expression analysis could improve diagnostic accuracy by delineating specific T-cell lymphoma classes or by identifying more precise prognostic models. 2,3 , 7-10 Nevertheless, the need for reliable diagnostic and prognostic markers in PTCL/AITL remains partially unmet.…”

Section: Introductionmentioning

confidence: 99%

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Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers

et al. 2021

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Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of around 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma, AITL; PTCL-with T follicular helper phenotype, PTCL-TFH; PTCL-not otherwise signified, PTCL-NOS) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH and PTCL-NOS. The main differences between the three nodal PTCL classes involved the RHOAG17V mutations (p<0.0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases, but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these three categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers

et al. 2021

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“…Genomic profiling showed that ALK+ ALCL displays a homogeneous cytotoxic/Th1 signature in contrast to ALK- ALCL that has either a cytotoxic profile or a Th2-associated signature. The TH2 group was enriched in cases displaying a DUSP22 rearrangement [ 25 ]. The presence of TP63 rearrangement in 12% of ALK- ALCLs defines a third ALCL category [ 2 ].…”

Section: Main Alcl Subtypesmentioning

confidence: 99%

Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas

Merlio

Kadin

2021

Cancers

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ALCL is a tumor of activated T cells and possibly innate lymphoid cells with several subtypes according to clinical presentation and genetic lesions. On one hand, the expression of transcription factors and cytokine receptors triggers signaling pathways. On the other hand, ALCL tumor cells also produce many proteins including chemokines, cytokines and growth factors that affect patient symptoms. Examples are accumulation of granulocytes stimulated by IL-8, IL-17, IL-9 and IL-13; epidermal hyperplasia and psoriasis-like skin lesions due to IL-22; and fever and weight loss in response to IL-6 and IFN-γ. In this review, we focus on the biology of the main ALCL subtypes as the identification of signaling pathways and ALCL-derived cytokines offers opportunities for targeted therapies.

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“…EGFRvIII identification was performed using ligationdependent reverse transcription polymerase chain reaction (LD-RT-PCR), which allows the detection of fusion transcripts and exon skipping [18][19][20]. RNA was extracted from FFPE tumor samples using the Maxwell® 16 LEV RNA FFPE Purification Kit (reference AS1260, Pro-mega®) and following manufacturer instructions.…”

Section: Ngs Experiments and Egfrviii Detectionmentioning

confidence: 99%

Simultaneous detection of EGFR amplification and EGFRvIII variant using digital PCR-based method in glioblastoma

Fontanilles

Marguet

Ruminy

et al. 2020

acta neuropathol commun

Self Cite

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Epidermal growth factor receptor (EGFR) amplification and EGFR variant III (EGFRvIII, deletion of exons 2-7) are of clinical interest for glioblastoma. The aim was to develop a digital PCR (dPCR)-based method using locked nucleic acid (LNA)-based hydrolysis probes, allowing the simultaneous detection of the EGFR amplification and EGFRvIII variant. Sixty-two patients were included. An exploratory cohort (n = 19) was used to develop the dPCR assay using three selected amplicons within the EGFR gene, targeting intron 1 (EGFR1), junction of exon 3 and intron 3 (EGFR2) and intron 22 (EGFR3). The copy number of EGFR was estimated by the relative quantification of EGFR1, EGFR2 and EGFR3 amplicon droplets compared to the droplets of a reference gene. EGFRvIII was identified by comparing the copy number of the EGFR2 amplicon to either the EGFR1 or EGFR3 amplicon. dPCR results were compared to fluorescence in situ hybridization (FISH) and next-generation sequencing for amplification; and to RT-PCR-based method for EGFRvIII. The dPCR assay was then tested in a validation cohort (n = 43). A total of 8/19 EGFR-amplified and 5/19 EGFRvIII-positive tumors were identified in the exploratory cohort. Compared to FISH, the EGFR3 dPCR assay detected all EGFR-amplified tumors (8/8, 100%) and had the highest concordance with the copy number estimation by NGS. The concordance between RT-PCR and dPCR was also 100% for detecting EGFRvIII using an absolute difference of 10.8 for the copy number between EGFR2 and EGFR3 probes. In the validation cohort, the sensitivity and specificity of dPCR using EGFR3 probes were 100% for the EGFR amplification detection compared to FISH (19/19). EGFRvIII was detected by dPCR in 8 EGFR-amplified patients and confirmed by RT-PCR. Compared to FISH, the EGFR2/EGFR3 dPCR assay was estimated with a one-half cost value. These results highlight that dPCR allowed the simultaneous detection of EGFR amplification and EGFRvIII for glioblastoma.

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Defining signatures of peripheral T-cell lymphoma with a targeted 20-marker gene expression profiling assay

Cited by 26 publications

References 31 publications

Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers

Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers

Cytokines, Genetic Lesions and Signaling Pathways in Anaplastic Large Cell Lymphomas

Simultaneous detection of EGFR amplification and EGFRvIII variant using digital PCR-based method in glioblastoma

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