Molecular cytogenetic abnormalities in multiple myeloma and plasma cell leukemia measured using comparative genomic hybridization

Abstract

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. Multiple 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 analyses that reduce subjectivity associated with identification of copy number changes and by requiring that sequence changes are visible using both red‐ and green‐labeled 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 sequence gain and loss than primary tumors. Regions of sequence copy number 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(17p11.2p13), and dim(6q22.1q23). Population distributions of genome‐wide changes in primary tumors reveal “hot‐spots” of sequence loss from 13q12.1‐q21, 13q32‐q34, 14q11.2‐q13, and 14q23‐q31. Genomic changes detected using CGH are consistent with those identified using banding analyses, although recurrent involvement of additional regions of the genome are also evident. A higher prevalence of genomic changes is visible 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 disease progression. Genes Chromosom. Cancer 19:124–133, 1997. © 1997 Wiley‐Liss, Inc.

Abnormalities on 1q and 7q are associated with poor outcome in sporadic Burkitt's lymphoma. A cytogenetic and comparative genomic hybridization study

“…Partial or full monosomy of 13 chromosome is usually found in B-cell chronic lymphocytic leukemia 36 and multiple myeloma patients. [37][38][39][40] In NHL, the frequencies of losses on 13q ranged from 4% in follicular lymphomas 23 to 49% in MCL. 7 Gains on 12q as well as losses on 13q have been reported as most frequent in cases with aggressive histopathologic features.…”

Interstitial del(14)(q) involving IGH: a novel recurrent aberration in B-NHL

“…The screening of 58 B-NHL cases with cytogenetic and/or FISH evidence of del(14)(q) led to identification of 13 additional cases with del(14)(q24.1q32.33), including one with the deletion masked by t(14;22)(q32;q11)/IGH-IGL (case 7). Additional FISH screening of 60 random CLL cases, seven MM cell lines, including four (RPMI-8226, L-363, OPM-1 and LP-1) with a previously described del(14), 2 and 20 various B-NHL cases with structural aberrations of 14q21-q24, failed to identify ZFP36L1 and/or IGH rearrangements, indicating that these deletions are rare molecular events.…”

Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy

“…Deletions of the long arm of chromosome 13 (13q−), mostly at the q14 site, and monosomy of chromosome 13 are commonly described in MM PC as determined by conventional metaphase analysis, [1][2][3] comparative genomic hybridization 4,5 and multicolor metaphase FISH (SKY). 6,7 Tricot and colleagues have associated the presence of 13q− with an adverse prognosis in patients with MM 8,9 and proposed this genomic abnormality as one of the most important prognostic factors for MM patients.…”