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01.07.2019 | Original Article

Comprehensive detection of chromosomal translocations in lymphoproliferative disorders by massively parallel sequencing

verfasst von: Philippe Szankasi, Ashini Bolia, Michael Liew, Jonathan A. Schumacher, Elaine P. S. Gee, Anna P. Matynia, K. David Li, Jay L. Patel, Xinjie Xu, Mohamed E. Salama, Todd W. Kelley

Erschienen in: Journal of Hematopathology | Ausgabe 3/2019

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Abstract

Balanced translocations have diagnostic and prognostic value in B-cell lymphoproliferative disorders (LPDs). Most of these translocations involve the juxtaposition of a strong immunoglobulin (Ig) enhancer to proto-oncogenes, such as BCL2, BCL6, and MYC, leading to their overexpression. These rearrangements generally do not result in mRNA fusions, and fluorescent in situ hybridization (FISH) remains the gold standard for assessing of recurrent translocations in LPDs. With the growing use of massively parallel sequencing for the detection of both point mutations and large structural rearrangements, we aimed at evaluating the utility of this method for the molecular work-up of B-cell LPDs side by side with FISH. We describe a method using solution capture for enrichment of known translocation breakpoints and massively parallel sequencing for the detection of balanced translocation in formalin-fixed tissues with a B-cell LPD. We detected a total of 57 rearrangements with a high concordance of 94.2% when compared to FISH. We detected translocations between BCL2, BCL6, and MYC and the three Ig loci and non-Ig loci, including novel partners for MYC and BCL6. In addition, massively parallel sequencing allowed a detailed analysis of the structure of the resulting chromosomal fusions. Our comparison shows the feasibility of using massively parallel sequencing for detecting balanced translocations in B-cell LPDs and advantages and disadvantages to both methods, and how they can complement each other.

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Titel: Comprehensive detection of chromosomal translocations in lymphoproliferative disorders by massively parallel sequencing
verfasst von: Philippe Szankasi
Ashini Bolia
Michael Liew
Jonathan A. Schumacher
Elaine P. S. Gee
Anna P. Matynia
K. David Li
Jay L. Patel
Xinjie Xu
Mohamed E. Salama
Todd W. Kelley
Publikationsdatum: 01.07.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Hematopathology / Ausgabe 3/2019
Print ISSN: 1868-9256
Elektronische ISSN: 1865-5785
DOI: https://doi.org/10.1007/s12308-019-00360-0

Springer Medizin

Comprehensive detection of chromosomal translocations in lymphoproliferative disorders by massively parallel sequencing

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

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