MOLECULAR CYTOGENETIC ABNORMALITIES IN MULTIPLE-MYELOMA AND PLASMA-CELL LEUKEMIA MEASURED USING COMPARATIVE GENOMIC HYBRIDIZATION

Comparative genomic hybridization (CGH) was used to identify recurrent regions of DNA sequence loss and gain in 21 multiple myeloma (MM) and plasma cell leukemia (PCL) primary tumor specimens and cell lines. Mu ltiple regions of non-random sequence loss and gain were observed in 8 /8 primary advanced stage tumors and 13/13 cell lines. Identification of sequence copy number changes was facilitated by statistical analyse s that reduce subjectivity associated with identification of copy numb er changes and by requiring that sequence changes are visible using bo th red- and green-labelled tumor DNA. Loss of sequence on 13q and 14q and gain of sequence on 1q and chromosome 7 occurred in 50-60% of the population. In general, cell lines carry more and larger regions of se quence gain and loss than primary tumors. Regions of sequence copy num ber change that recur among MM cell lines and primary tumors include, in order of prevalence, enh(1q12qter), dim(13), enh(7), enh(3q22q29), enh(11q13.3qter), dim(14q11.2q31), enh(8q21qter), enh(3p25pter), dim(1 7p11.2p13), and dim(6q22.1q23). Population distributions of genome-wid e changes in primary tumors reveal ''hot-spots'' of sequence loss from 13q12.1-q21, 13q32-q34, 14q11.2-q13, and 14q23-q31. Genomic changes d etected using CCH are consistent with those identified using banding a nalyses, although recurrent involvement of additional regions of the g enome are also evident. A higher prevalence of genomic changes is visi ble using CGH compared to banding. Identification of recurrent regions of sequence gain and loss provides opportunities to identify regions of the genome that may be involved in the malignant phenotype and/or d isease progression. (C) 1997 Wiley-Liss, Inc.