Fluorescence in situ hybridization panel for monitoring of minimal residual disease in patients with double minute chromosomes

Blood Cells Mol Dis. 2014 Apr;52(4):208-13. doi: 10.1016/j.bcmd.2013.10.008. Epub 2013 Nov 7.

Abstract

A double minute chromosome (dmin) is a small fragment of extrachromosomal DNA bearing amplified genes observed in malignancies. We investigated the incidence and characteristics of dmins in hematologic malignancies, and the quantitative changes during the treatment follow-up. Once a dmin was observed in conventional G-banding, it was characterized using fluorescence in situ hybridization (FISH) with the panel of MYC, NMYC, and MLL probes. Quantitative changes of malignant cells were measured using G-banding and FISH during the follow up. Dmins were observed in 1.23% of patients (6/489) at the initial diagnosis including 4 with MYC amplification, 1 with MLL and 1 with NMYC. All 6 had complex karyotypes and showed short overall survival (7.7 months). In follow-up specimens, FISH detected dmins in 11 cases out of which G-banding detected dmins in 9 cases. The number of dmins detected by FISH and G-banding did not correlate well. Amplification of NMYC in dmins is reported for the first time. A FISH panel composed of frequently amplified oncogenes (MYC, NMYC, and MLL) in dmins is useful for characterization of dmins. FISH is a sensitive method in detecting dmins and will be useful in monitoring of the minimal residual disease.

Keywords: Double minute chromosome; Fluorescence in situ hybridization; NMYC; Oncogene.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Marrow / pathology
  • Child
  • Chromatin*
  • Chromosome Aberrations*
  • Chromosome Banding
  • Fatal Outcome
  • Female
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / pathology*
  • Hematologic Neoplasms / therapy
  • Humans
  • In Situ Hybridization, Fluorescence*
  • Karyotype
  • Male
  • Middle Aged
  • Neoplasm, Residual / diagnosis*
  • Treatment Outcome
  • Young Adult

Substances

  • Chromatin