Unexpected favorable outcome in a patient with high grade B-cell lymphoma with abnormalities of MYC, BCL6 and BCL2 loci

Thomas Adams, Deborah Fuchs, Patricia K. Shadoan, Laurel Johnstone, Branden M. Lau, Lee McGhan, Faiz Anwer, Hussam Al-Kateb

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

High grade B-cell lymphoma (HGBCL) by WHO 2016 classification requires rearrangements of MYC and BCL2 and/or BCL6, practically covering the so called “double-hit” or “triple hit” lymphomas. We report a case of HGBCL “triple-hit” lymphoma in a 64-year old female. Cytogenetic and fluorescence in situ hybridization (FISH) studies revealed complex karyotype including rearrangement of MYC to a novel, non-IG partner on chromosome 18, and rearrangement of BCL2, BCL6 and IGH as well as ins(3)(q21q27.3q25.1) among other abnormalities. FISH studies showed five copies of MYC and 3–8 copies of BCL2. Gene expression analysis by RNA sequencing showed that MYC, BCL2 and MECOM genes were overexpressed whereas BCL6 was under-expressed. BCL6 was fused to MBNL1 gene due to complex structural rearrangement. MYC was expressed in >70% of cells and BCL2 was diffusely but highly expressed by immunohistochemistry. No pathogenic mutations were identified by sequencing a 26-gene panel including TP53. The patient has unexpectedly been in complete remission for 12 months after diagnosis after intensive chemotherapy including DA-EPOCH regimen despite having HGBCL. The prognostication of HGBCL patients may further be improved by the sub-categorization of these lymphomas on the basis of more detailed genomic markers than merely the WHO 2016 classification.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalCancer Genetics
Volume222-223
DOIs
StatePublished - Apr 2018

Keywords

  • Double hit lymphoma
  • High grade B-cell lymphoma
  • MYC translocation
  • MYC translocation to non-IG
  • Prognostication of HGBCL
  • Triple hit lymphoma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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