Bacterial artificial chromosome array-based comparative genomic hybridization using paired formalin-fixed, paraffin-embedded and fresh frozen tissue specimens in multiple myeloma.
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.
Lennon
Patrick A
PA
School of Health Sciences, Department of Hematopathology, the University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Zhuang
Yi
Y
Pierson
Diane
D
Zhang
Xiang
X
Williams
Chris
C
Perez
Cintia
C
Lin
Pei
P
D000368:Aged; D001854:Bone Marrow Cells; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D005629:Frozen Sections; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D016612:Paraffin Embedding / Q000379:methods; D046888:Tissue Array Analysis