The prognostic significance of cytogenetics and molecular profiling in multiple myeloma

Representative partial karyotypes of metaphase chromosomes demonstrating the different types and degrees of amplification of chromosome 1. FISH probes for 1q12 (red), 1q21 (green), and 16q11 (aqua) are shown on inverted DAPI images of chromosomes depicting G-band patterns. (A) Chromosome 1 pair showing interstitial deletion of 1p (arrow) in the homologue on left and a direct dup1q12∼q23 on chromosome 1 on the right. Note two copies of probes satII/III and 1q21 (arrows) on the duplicated 1. (B) Chromosomes 1 showing the normal homologue on the left and the abnormal homologue on the right, demonstrating both an interstitial deletion of 1p (arrow) and amplification of 1q in the same chromosome. Note four copies of 1q21 (arrows) in an inverted duplication pattern. (C) Example of an unbalanced whole-arm translocation of 1q to chromosome 16q. Chromosomes 1 are on the left, and chromosomes 16 on the right. Aqua probe denotes 16q11 heterochromatin. Note the loss of 16q distal to the aqua probe on the der(1;16)(q10;p10). The entire long arm 1q is translocated to the pericentromeric region of 16q, and a total of three copies of 1q21 (arrows) are present. (D) Example of an unbalanced whole-arm translocation of 1q to 19q. Note that the result of this translocation is the der(1;19)(q10;p10) chromosome, which shows an extra copy of 1q21 (arrows) and loss of the entire 19q. (E) Example of jumping 1q, in which all or part of 1q is translocated to three different receptors, including chromosomes 19, 21, and 22. Note the inverted duplication (dup) on chromosome 1 (second from left) and copies of 1q (arrows) on the three different nonhomologous chromosomes. The whole-arm der(19)(q10;p10) in this case is the same type seen in the patient in (D). The der(21) results from a segmental translocation of the inverted dup of 1q to the short arm of the 21. The der(22) results from a whole-arm 1q translocated to short arm of 22. (F) Homologues of chromosome 1 demonstrating amplification of 1q12∼q23 by breakage-fusion-bridge (BFB) cycles. Note multiple copies of 1q21 (arrows) on the abnormal homologue on the right. The copies of the 1q12∼q23 amplicon occur in an inverted repeat pattern, with a deletion of the 1q distal to the amplified region. Dotted lines between normal homologue 1 (left) and abnormal homologue denote the size of expansion of the 1q12∼q23 region by BFB cycles.

Summary of genomic profiles and recurrence of chromosomal alterations in primary tumors demonstrated by aCGH. The recurrence plot mirrors the frequencies of previously reported chromosomal gains and losses, including the deletions of 1p and amplifications of 1q. Integer-value recurrence of copy number aberrations across the samples in segmented data is plotted on the y axis. The x axis is in chromosomal order. Dark red or green bands denote the number of samples with gain or loss of chromosome material, and bright red or green bars represent the number of samples showing amplification or deletion. Asterisks show focal deletions of the kappa (2p;12), IgH (14q32), and lambda chain (22q11) loci physiological in B cell postgerminal center neoplasms [used with permission, Carrasco et al. (71)].