Use of plasma DNA in detection of loss of heterozygosity in patients with multiple myeloma.
BACKGROUND
Deletions or structural abnormalities in chromosomes 11 and 13 have been shown to be important in predicting clinical behavior in patients with multiple myeloma (MM). However, cytogenetic analysis in MM is frequently difficult because of poor yield of informative metaphases and the disease is frequently patchy, which complicates fluorescent in situ hybridization studies.


OBJECTIVE
The purpose of this study was to explore the potential of using peripheral plasma DNA for the detection of loss of heterozygosity (LOH) in chromosomes 11 and 13 in patients with MM.


METHODS
Peripheral blood (PB) plasma of 81 patients with MM, was used as a source of DNA for the detection of LOH at chromosomes 13q14 (D13S319 and D13AFMaw301wb5), and 11q21 (D11S2179) using polymerase chain reaction.


RESULTS
Only 62 of the studied patients were informative for the two 13q microsatellite markers and 16 (26%) of these patients showed LOH. Only seven (11%) of 61 patients with informative D11S2179 microsatellite maker showed LOH. Purified plasma cells (PCs) from six bone marrow (BM) samples using anti-CD138-coated magnetic beads showed identical results to those detected in DNA isolated from PB plasma. Three patients with LOH underwent autologous BM transplantation, and two of three reverted to a normal state (no LOH) after transplantation. Seven of the patients with 13q LOH in PB plasma had <10% PCs (PCs) in their BM at the time of testing.


CONCLUSIONS
PB plasma appears to be enriched by tumor-specific DNA and can be used to detect chromosomal abnormalities in patients with MM. Further studies are needed to establish the clinical relevance of this approach in comparison with other techniques.
Ahmed
Maha
M
Department of Hematopathology, M.D. Anderson Cancer Center, The University of Texas, Houston, TX 77030-4095, USA.
Giles
Francis
F
Joe
Youngson
Y
Weber
Donna M
DM
Jilani
Iman
I
Manshouri
Taghi
T
Giralt
Sergio
S
De Lima
Marcos
M
Keating
Michael
M
Albitar
Maher
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D004247:DNA / Q000097:blood*; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis
D004247:DNA