Bacterial artificial chromosome array-based comparative genomic hybridization using paired formalin-fixed, paraffin-embedded and fresh frozen tissue specimens in multiple myeloma

Cancer. 2009 Jan 15;115(2):345-54. doi: 10.1002/cncr.24021.

Abstract

Background: Multiple myeloma (MM) is a neoplasm of malignant plasma cells that often harbors many chromosomal aberrations. Currently, fresh frozen tissues (FT) are considered the most reliable for molecular genetic analysis; however, formalin-fixed, paraffin-embedded (FFPE) tissues are easily retrievable. Compared with conventional cytogenetics, bacterial artificial chromosome (BAC) array-comparative genomic hybridization (CGH) allows more sensitive detection of chromosomal abnormalities.

Methods: The authors analyzed 7 paired FT and FFPE samples of bone marrow aspirate materials obtained from patients with MM in parallel to determine the efficacy of BAC array-CGH using FFPE.

Results: Thirty-four aberrations were identified, including 29 that were observed in both sample types, yielding 85% concordance. Nonrandom anomalies, including gains on 7q, 9q, 15q, and 19p and losses on 8p and 13q, were observed in paired samples from at least 2 patients. To verify these results, fluorescence in situ hybridization (FISH) was performed using probes specific for 7q and 15q, and gains were observed in the 4 samples that were examined. Furthermore, 1 of 3 samples from patients who had monoclonal gammopathy of undetermined significance that were tested also carried gain on 7q, suggesting that this aberration may be an early transforming event.

Conclusions: The current results indicated that BAC array-CGH can be effective using FFPE samples and is a sensitive method for the identification of nonrandom chromosomal aberrations in MM.

Publication types

  • Evaluation Study

MeSH terms

  • Aged
  • Bone Marrow Cells
  • Chromosome Aberrations
  • Chromosomes, Artificial, Bacterial*
  • Comparative Genomic Hybridization / methods*
  • Female
  • Frozen Sections
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Multiple Myeloma / genetics*
  • Paraffin Embedding* / methods
  • Tissue Array Analysis