Identification of a novel e8/a4 BCR/ABL fusion transcript in a case of a transformed Sezary syndrome

Callet‐Bauchu, Evelyne; Salles, Gilles; Gazzo, Sophie; Dalle, S.; Berger, Françoise; Hayette, Sandrine

doi:10.3324/haematol.11341

Cited by 4 publications

(2 citation statements)

References 7 publications

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“…In patient SS15, we observed a fusion gene involving BCR-NDUFAF6. A BCR-ABL fusion transcript involving exon 8 and exon 4, respectively, has been reported in a SS patient (Callet-Bauchu et al, 2007). Table 1 summarizes the key somatic genomic changes across 15 patients.…”

Section: Fusion Eventsmentioning

confidence: 99%

Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome

Prasad

Rabionet

Espinet

et al. 2016

Journal of Investigative Dermatology

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Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma with an aggressive clinical course. The genetic etiology of the disease is poorly understood, with chromosomal abnormalities and mutations in some genes being involved in the disease. The goal of our study was to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sézary cells, 14 of them fulfilling the diagnostic criteria of Sézary syndrome. We have discovered genes that could be involved in the pathogenesis of Sézary syndrome. Some of the genes that are affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and RAG2, with some of them mutated in more than one patient. We observed several somatic copy number variations shared between patients, including deletions and duplications of large segments of chromosome 17. Genes with potential function in the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sézary syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1. Furthermore, we discovered several fusion events of interest involving RASA2, NFKB2, BCR, FASN, ZEB1, TYK2, and SGMS1. Our work has implications for the development of potential therapeutic approaches for this aggressive disease.

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Section: Fusion Eventsmentioning

confidence: 99%

Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome

Prasad

Rabionet

Espinet

et al. 2016

Journal of Investigative Dermatology

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“…1 These transcripts are well-characterized and frequently detected by screening methods based on real-time quantitative RT-PCR (qRT-PCR), which is considered as the gold standard for the diagnostic and follow-up examination of Ph positive leukemia due to its superior sensitivity and cost-effectiveness. 2 However, new and rare forms of BCR-ABL1 fusions have also been discovered and these novel fusion gene variants including those with a masked or undetermined Ph chromosome karyotyping, often cannot be identified by routine RT-PCR methods, [3][4][5][6][7][8][9][10][11][12][13][14][15] presenting a big challenge for conventional diagnostic approaches.…”

Section: Introductionmentioning

confidence: 99%

Novel BCR-ABL1 fusion and leukemic mutations of SETBP1, PAX5, and TP53 detected by next generation sequencing in chronic myeloid leukemia

et al. 2016

Cancer Biology & Therapy

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Patients with BCR-ABL1 fusion genes are potential candidates for targeted therapy with tyrosine kinase inhibitor (TKI) imatinib. However, novel BCR-ABL1 fusion variants can be undetected by qRT-PCR-based routine molecular screening, affecting immediate patient management and proper treatment selection. In this study, we describe a case of chronic myeloid leukemia (CML) harboring a novel BCR-ABL1 variant gene. Although Fluorescent In situ Hybridization (FISH) analysis suggested Philadelphia (Ph) translocation, qRT-PCR screening failed to detect the presence of a functional fusion transcript, which is critical for selecting targeted therapy against BCR-ABL1 fusion with aberrant kinase activity. Meanwhile, G-band cytogenetic analysis was performed twice without a solid conclusion. To overcome the uncertainty whether TKIs should be used to treat this patient effectively, we performed whole genome sequencing (WGS) in a next-generation sequencing (NGS) platform and discovered an unusual e13a2-like BCR-ABL1 fusion with 9 ABL1 intron 1 nucleotides incorporated into the broken BCR exon 13 to form a novel chimeric exon, which has never been described previously based on the best of our knowledge. Based on FISH and NGS results, the patient was treated with imatinib, showing significant improvement. Moreover, we also detected novel genetic mutations in the known leukemic genes SETBP1, PAX5, and TP53, while their role in the leukemogenesis remains to be determined. In summary, we have identified BCR-ABL1 fusion and other genetic mutations in a diagnostically difficult case of CML, demonstrating that NGS is a powerful diagnostic tool when routine procedures are challenged.

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Novel BCR-ABL1 fusion identified by targeted next-generation sequencing in a patient with an atypical myeloproliferative neoplasm

2014

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Identification of a novel e8/a4 BCR/ABL fusion transcript in a case of a transformed Sezary syndrome

Cited by 4 publications

References 7 publications

Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome

Identification of Gene Mutations and Fusion Genes in Patients with Sézary Syndrome

Novel BCR-ABL1 fusion and leukemic mutations of SETBP1, PAX5, and TP53 detected by next generation sequencing in chronic myeloid leukemia

Novel BCR-ABL1 fusion identified by targeted next-generation sequencing in a patient with an atypical myeloproliferative neoplasm

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