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Journal of Hematopathology

, Volume 12, Issue 3, pp 121–133 | Cite as

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

  • Philippe SzankasiEmail author
  • 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
Original Article
  • 30 Downloads

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.

Keywords

Chromosomal translocation Massively parallel sequencing B-cell lymphoma VDJ recombination 

Notes

Funding

This study was supported by the Association for Regional and University Pathologists (ARUP) Laboratories, Salt Lake City, UT.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12308_2019_360_MOESM1_ESM.pdf (474 kb)
ESM 1 (PDF 474 kb)
12308_2019_360_MOESM2_ESM.xlsx (15 kb)
ESM 2 (XLSX 15 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Philippe Szankasi
    • 1
    Email author
  • Ashini Bolia
    • 1
  • Michael Liew
    • 1
  • Jonathan A. Schumacher
    • 1
  • Elaine P. S. Gee
    • 1
    • 2
  • Anna P. Matynia
    • 1
    • 3
  • K. David Li
    • 1
    • 3
    • 4
  • Jay L. Patel
    • 1
    • 3
  • Xinjie Xu
    • 1
    • 3
  • Mohamed E. Salama
    • 1
    • 3
    • 5
  • Todd W. Kelley
    • 1
    • 3
    • 6
  1. 1.ARUP LaboratoriesSalt Lake CityUSA
  2. 2.BigHead Analytics GroupWindsorUSA
  3. 3.Department of PathologyUniversity of UtahSalt Lake CityUSA
  4. 4.Department of PathologyUniversity of WashingtonSeattleUSA
  5. 5.Mayo ClinicRochesterUSA
  6. 6.NavicanSalt Lake CityUSA

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