Multicolour spectral karyotyping identifies new translocations and a recurring pathway for chromosome loss in multiple myeloma - Sawyer - 2001 - British Journal of Haematology - Wiley Online Library Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URLShare a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Multicolour spectral karyotyping (SKY) was performed on primary tumour specimens from 100 patientswith multiple myeloma (MM) that showed complex clonal chromosome aberrations not fully characterized by G-banding. In this study, SKY was able to identify or revise translocations with breakpoints involving 14q32, 11q13 or 8q24 in 32 patients (32%). Five new recurring translocations were identified, two of which involved chromosome 22. A subtle reciprocal translocation t(14;22) (q32;q11∼12) was identified using SKY in two patients and a second, much larger, translocation t(11;22)(q13;q13) was identified using G-banding in three patients. A third new translocation was identified in two patients using SKY and G-banding as der(7)t(7;7)(p15∼22;q22∼32). Twenty-three patients (23%) showed the loss of 8p by whole-arm translocations with different whole-arm donor chromosomes. Among this group, two new recurring whole-arm translocations involving the centromeric breakpoint 8q10 were identified as der(8;20)(q10;q10) and der(8;18) (q10;q10) in three patients each. In addition, a novel pattern of three-way translocations involving the clonal evolution of the t(8;22)(q24;q11) by the subsequent loss of 8p by whole-arm translocations was found in three patients. The chromosome instability identified here demonstrates that the loss of 8p can occur by multiple whole-arm translocations, indicating a new pathway for the loss of a specific chromosome region in MM. Karyotypes in multiple myeloma (MM) typically show multiple complex rearrangements involving a number of different chromosomes during the course of tumour progression. The complexity of these karyotypes has proved problematic for chromosome banding techniques and, in many cases, the aberrations cannot be fully characterized (DeWald etal, 1995; Sawyer etal, 1995; Calasanz etal, 1997). The molecular cytogenetic techniques of multicolourfluorescence in situ hybridization (M-FISH) and multicolour spectral karyotyping (SKY) can provide significantly more information because they allow the display ofeach chromosome in a different colour and, thus, makepossible the identification of chromosomal bands ofunknown origin, including translocations, insertions, complex rearrangements and marker chromosomes (Schrock etal, 1996; Speicher etal, 1996). SKY has been shown to identify hidden chromosome abnormalities in many different types of haematological malignancies and solid tumours (Veldman etal, 1997), and recent reports indicate that, when analysed by molecular cytogenetic techniques, MM is even more karyotypically complex than previously thought (Rao etal, 1998). With the use of G-banding, chromosome bands 14q32 (IGH), 11q13 (BCL-1/cyclin D1) and 8q24 (C-MYC) are the most frequently reported breakpoints in myeloma. However, in suboptimal specimens, the poor morphology of the chromosomes in MM precludes the accurate identification of translocation partners, especially in relation to the add(14)(q32) chromosome. Therefore, with G-band karyotype analysis, many of these smaller complex aberrations can only be described with imprecise interpretations such as the ‘add’ designation. It has recently been shown that several recurring translocations in MM are very difficult orimpossible to detect using conventional cytogenetics. Forexample, with cytogenetic techniques, the t(14;20) (q32;q11), t(14;16)(q32;q23) and t(9;14)(p12;q32) have only been reported by SKY, and, at the cytogenetic level, the t(4;14)(p16;q32) can only be identified by FISH (Chesi etal, 1997, 1998; Ida etal, 1997; Sawyer etal, 1998a; Finelli etal, 1999). There appear to be at least 10 different recurring translocation partners for the IGH locus found using classical cytogenetics and molecular techniques, several of which are similar to those seen in other B-cell disorders (Bergsagel etal, 1996). This multiplicity of the IgH translocations suggests that, although these are almost universal events in MM, their importance in the pathogenesis remains unclear (Bergsagel etal, 1996; Hallek etal, 1998). It is therefore important to search the complex karyotypes for other new cytogenetic aberrations that may have diagnostic or prognostic significance. Here, we report SKY results on 100 complex abnormal karyotypes that identify new reciprocal translocations and new whole-arm translocations, and provide insights on the progression of secondary chromosome aberrations in MM. Sample selection was based on specimens showing clonally abnormal karyotypes with chromosome aberrations that were not fully characterized by G-banding. Therefore, cases identified by G-banding involving a clear t(11;14)(q13;q32) translocation were excluded from analysis unless additional unidentified aberrations involving breakpoints of special interest, such as add(8q24), del(16)(q22) or der(22), were involved. Bone marrow aspirates of 100 patients were processed for routine chromosome studies as previously described (Sawyer etal, 1995). An abnormal clone was identified as two or more metaphases displaying either the same structural abnormality or the same extra chromosome or at least three cells with the same missing chromosome. Aberrations were designated according to ISCN (1995). Chromosome aberrations ascertained by SKY were assigned breakpoints if the aberrations were identified in two or more cells and if the comparison of 4,6-diamidino-2-phenyl-indole (DAPI)-banding of the same metaphase corresponded with the G-banding of other metaphase cells. A breakpoint was considered recurring if identified in two or more specimens using G-banding or SKY. SKY methods The SKY probe mixture and hybridization reagents were prepared by Applied Spectral Imaging (Carlsbad, CA, USA). SKY and FISH procedures were performed as previously described (Sawyer etal, 1998a). Briefly, the chromosome painting probes were generated, as described elsewhere, by flow sorting human chromosomes and DNA amplification using degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) (Telenius etal, 1992). A combination labelling of five fluorochromes, including various combinations of rhodamine, spectrum green, Texas red, spectrum orange, Cy5 and Cy5·5, were used to generate the 24 colours. Slides for spectral karyotyping were treated basically according to the manufacturer\'s protocol with the probe cocktail hybridized to the slides for 2 d at 37°C. Chromosomes were counterstained with DAPI/anti-fade solution. Image acquisition was performed using a SD200 Spectracube (Applied Spectral Imaging) mounted on a Zeiss Axioplan II microscope using a custom-designed optical filter (SKY-1, Chroma Technology, Brattleboro, VT, USA) that allows for simultaneous excitation of all dyes and measurement of their emission spectra. The DAPI images were used in conjunction with spectral classifications and G-banding for the identification of chromosome aberrations. FISH analysis Conventional dual-colour whole chromosome painting probes (Vysis, Downers Grove, IL, USA) for chromosomes 6, 8, 11, 14, 16, 20 and 22 were used according to the manufacturer\'s protocol to confirm recurring translocations in the analysis of the add(14)(q32) chromosomes (not shown). One hundred patient samples showing complex karyotypes using routine G-banding that could not be completely resolved were subsequently reanalysed with spectral karyotyping for the presence of new, previously unidentified translocations. In all cases, SKY either confirmed or resolved at least one aberration that could not be identified using G-banding. The SKY technique identified or refined G-band chromosome aberrations involving 11q13, 14q32, 7p22, 8q24 and 8p11 to recurring translocations in 41 patients (40%) (Table I). Twenty-six translocations involving breakpoints of 11q13, 14q32, 8q24 and 22q12 were confirmed by SKY (Table II). Five new translocations were identified as t(14;22)(q32;q11∼12) (Fig 1A), t(11;22) (q13;q13)(Fig 1B), der(7)t(7;7)(p15∼22;q22∼32) (Fig 1C), der(8;20)(q10;q10) (Fig 1D) and der(8;18)(q10;q10) (Fig 1E). Table 1. Recurring chromosome aberrations using G-banding and refined designations using spectral karyotyping. Table II. Recurring chromosome aberrations of 14q32, 8q24 and 22q11∼13 identified using G-banding and confirmed using SKY. Partial karyotypes from six different patients demonstrating recurring translocations using SKY and G-banding. Each row (A–F) represents a different patient sample, with brackets within each row indicating a different representation of the same aberration. Chromosomes are presented in SKY display colours (left brackets), SKY classification colours (centre brackets) and G-banding (right brackets). A. Patient sample No. 12 demonstrates translocation t(14;22)(q32;q11∼12). B. Patient sample No. 6 demonstrates t(11;22)(q13;q13). C. Patient sample No. 18 demonstrates der(7)t(7;7)(p15∼22;q22∼32). D. Patient sample No. 39 demonstrates t(8;20)(q10;q10). E. Patient sample No. 71 demonstrates t(8;18)(q10;q10). F. Patient sample No. 32 demonstrates der(8)t(6;8)(p10;q10)t(8;22)(q24;q11). Arrows on G-banded chromosomes indicate breakpoints. Thirty-eight patients showed aberrations of 14q32 using G-banding. The largest group of 18 specimens was designated as add(14q32) using G-banding. Three of these were refined to t(8;14)(q24;q32) (Nos. 30, 77 and 97), two as (6;14)(p21;q32) (Nos. 7 and 48), two as t(14;22)(q32;q11∼q12) (Nos. 12 and 34)(Fig 1A) and one as t(14;16)(q32;q22) (No. 33) (Table I). The remaining 10 showed non-recurring aberrations. Of 18 patients correctly identified using G-banding, seven patients showed t(11;14)(q13;q32) (Nos. 13, 20, 29, 46, 53 and 69), four had t(14;16)(q32;q22) (Nos. 31, 59, 77 and 85), three showed t(6;14)(p21;q32) (Nos. 73, 76 and 92), two had t(8;14)(q24;q32) (Nos. 49 and 51) and two showed t(1;14)(q10;q32) (Nos. 1 and 54) (Table II). Six patients identified using G-banding as t(8;14)(q24;q32) were refinedby SKY to two patients each with t(14;20) (q32;q11) (Nos. 37 and 55) and t(14;16)(q32;q22) (Nos. 10 and 25) (Table I). The remaining two showed non-recurring translocations. Seven specimens showed the t(11;14)(q13;q32), as described above. A second translocation involving the 11q13 breakpoint was identified as t(11;22)(q13;q13) using G-banding and SKY in three patients (Fig 1B). A t(8;11)(q24;q13) was found in one patient and has also been identified in a previous study (Sawyer etal, 1998a). Twenty patients showed recurring translocations involving 8q24 using G-banding. These included seven with t(8;22)(q24;q12), five identified using G-banding (Nos. 17, 19, 37, 54 and 76) (Table II) and two identified using SKY(Nos. 32 and 72) (Table I). Four patients with t(1;8) (p13;q24) were identified using G-banding (Nos. 15, 59 and 87) (Table II) and one identified by SKY (No. 23) (Table I). Two patients with t(8;14)(q24;q32) and two patients with t(2;8)(p12;q24) were identified using G-banding. Six specimensoriginally designated as t(8;14)(q24;q32) using G-banding were refined by SKY as described above in the 14q32 aberration section. Thirty-nine patients showed loss of all or part of 8p. This included 14 patients showing monosomy 8, 23 patients showing loss of the entire 8p by whole-arm translocations and two patients showing deletion of 8p21. Two new whole-arm translocations involving the 8p10 breakpoint were identified. The der(8;20)(q10;q10) (Fig 1D) was found in three patients (Nos. 39, 60 and 73) (Table I). The other new translocation, der(8;18)(q10;q10) (Fig 1E), was also found in three patients (Nos. 54, 71 and 74)(Table I). Seventeen additional patients showed whole-arm translocations resultingin the loss of 8p. These included two each with the previously reported whole-arm translocations der(6;8)(p10;q10), der(8;9)(q10;q10), i(8)(q10) and one with der(8;12)(q10;q10). Ten patients showed different whole-arm exchange partners with breakpoints at 8q10. In addition, three-way translocations involving the clonal evolution of the classic t(8;22)(q24;q11) by the subsequent loss of 8p by whole-arm translocations were identified in three patients in three different variations. The loss of 8p resulted in a der(6;8)(p10;q10) t(8;22)(q24;q11) (Fig 1F), a der(8;9)(q10;q10)t (8;22) (q24;q11) and a der(8;18)(q10;q10)t(8;22)(q24;q11), indicating that this secondary aberration occurs in a number of combinations. Eleven patients showed unbalanced translocations with breakpoints of 8p11∼23. Three of these unbalanced translocations involved translocations of 8p21∼22 with different segments of the X chromosome. Fifty-six whole-arm translocations of 1q were noted, 10 of which occurred in more than one patient. These whole-arm translocations involve the gain of an entire 1q translocated to a non-homologous chromosome. In decreasing order of frequency (excluding chromosome 16, discussed below) these include seven patients with t(1;6)(q10;p10), four with t(1;19)(q10;p10), three each with t(1;15)(q10;q10), two each with t(1;14)(q10;q32), t(1;2)(q10;q37), t(1;5)(q10;p10), t(1;8)(q10;p10), t(1;9)(q10;p10), t(1;17)(q10;p13) or t(1;22) (q10;q10). Duplications of the chromosome regions 1q10∼32 were found in six patients. Recurring deletions of all or part of chromosome 1p were identified in 21 patients, with the most frequently deleted segment being 1p13∼32. The recurring t(1;8)(p13;q24) was identified in four patients. Fifty-four patients showed monosomy or deletion 13. Forty-six patients showed monosomy 13, eight patients showed deletion 13 and five patients showed translocations of 13, although none were recurring. Monosomy for chromosome 16 was found in 13 patients and deletions of 16 q22 occurred in 16 patients. Twenty-two patients showed translocations involving 16q. The t(14;16)(q32;q22) was found in seven patients (see above). Ten patients showed translocations between the long arm of chromosome 1 and chromosome 16, including t(1;16) (q10;p10), t(1;16)(q11;q12∼22) and t(1;16)(q21;q22∼q23). The cytogenetic analysis of the multiple complex chromosome aberrations found in MM has proved difficult with traditional techniques. In this study, we have identified both new balanced reciprocal translocations and characterized anew pathway for the loss of chromosome 8p. A subtle newtranslocation has emerged from the analysis of the add(14)(q32) chromosomes in this study and was designated as t(14;22)(q32;q11∼12) (Fig 1A). SKY analysis refined the karyotype of another patient originally designated using G-banding as t(14;16)(q32;q22) to the designation t(14;22)(p13;q12∼13). These cases re-emphasize the usefulness of the SKY technique in identifying subtle translocations. This new t(14;22)(q32; q11∼12) translocation appears at the G-banding level to be similar to a translocation that has been previously reported in acute lymphoblastic leukaemia (ALL). The interpretation of this translocation in ALL is that the t(14;22) is a variant of the t(9;22)(q34;q11) (de Klein etal, 1986). Therefore, this is probably a secondary aberration in MM and further extends previous studies, suggesting ‘promiscuous’ translocations to the IgH locus at 14q32 (Bergsagel etal, 1996). The second new reciprocal translocation to emerge from this study involves the 11q13 breakpoint commonly found in MM. The 11q13 breakpoint (Cyclin-D) in this reciprocal translocation exchanges with 22q13. Surprisingly, to our knowledge, the t(11;22)(q13;q13) has not previously been reported in MM, but has been reported in acute erythroleukaemia (Gibbons etal, 1994). The 22q13 breakpoint in this translocation is distal to the Ig lambda locus at 22q11. Therefore, the significance of this translocation of 11q13 in MM is unclear and remains to be investigated at the molecular level. Two lines of evidence for a second recurring region of deletion (in addition to del13) were found. First, the loss of 8p, by either monosomy 8 or deletion of 8p (partial deletion or whole-arm loss), occurred in nearly half of the samples (48%). This represents only slightly fewer patients than those identified with the loss or deletion of chromosome 13 (54%). Secondly, a distinctive breakpoint at 8q10 has emerged in this study which involves the loss of 8p by multiple unbalanced translocations. The mechanism involves the whole-arm loss by centric fission at 8q10 and subsequent refusion at 8q10 with various donor chromosome arms. Whole-arm translocations involving 8q10 were found to occur both as stable clonal rearrangements alone or as a progressive step secondary to a chromosome 8 already exhibiting a t(8;22)(q24;q11) translocation. The t(8;22)(q24;q11) was identified in a total of seven patients; interestingly, three of these patients (Nos. 19, 32 and 54), showed the clonal evolution of the t(8;22)(q24;q11) translocation chromosome. In these three patients, a three-way unbalanced translocation subsequently evolved from a t(8;22)(q24;q11). In patient 19, the 8p was replaced by 9q, in patient 32, the 8p was replaced by 6p (Fig 1E), and in patient 54, the 8p was replaced by 18q (Fig 2). These findings indicate that, in MM, both an oncogene rearrangement as a result of the t(8;22)(q24;q11) and the subsequent loss of a putative tumour suppressor gene (by loss of 8p) can occur to the same chromosome 8. With SKY, in this and a previous SKY study (Sawyer etal, 1998a), we have identified three recurring whole-arm translocations, including der (6;8)(q10;q10), der(8;18)(q10;q10) and der(8;20)(q10;q10), which result in the loss of the entire 8p. Studies of loss of heterozygosity (LOH) have demonstrated that loss of 8p is detected in many tumour types, including breast, prostate and ovarian cancers (Wright etal, 1998; Perinchery etal, 1999; Yokota etal, 1999). At least two candidate tumour suppressor genes have been mapped to 8p including DLC-1 and FEZ1 (Yuan etal, 1998; Ishii etal, 1999). Characterization of a pathway for the loss of chromosome 8p in the progression of karyotype aberrations in MM. Two related types of aberrations have been observed, those that involve only whole-arm 8p translocations (top) and those that involve whole-arm translocations secondary to the evolution of a t(8;22)(q24;q11) (bottom). Chromosomes 8 usually appear normal (A) in myeloma or show a classical 8q24 translocation such as the t(8;22)(q24;q11) (B). However, during karyotype evolution, the integrity of the pericentromeric region of chromosome 8q10 is somehow disrupted, resulting in centric fission (C) and loss of 8p. Subsequent refusion of 8q occurs with a donor chromosome arm (D), resulting in stable subclones. In one case (No. 32), subclones emerged in which another round of fission (E) and fusion further altered the der(6;8)(p10;q10)t(8;22)(q24;q11) into an i(8)(q10)t(8;22)(q24;q11)(F). The identification of the new recurring pathway for the loss of chromosome 8p demonstrated here indicates that two related patterns of chromosome imbalance resulting in the gain and loss of specific chromosome arms have been identified in MM. Previously, we have described the gain of a specific chromosome arm by at least 10 different whole-arm translocations of 1q. These translocations are a product of chromosome instability and result in the gain of multiple copies (amplification) of the 1q chromosome region (Sawyer etal, 1998b; Dascalescu etal, 1999). The gain of 1q and lossof 8p are examples of chromosome exchanges (whole arm-translocations) that produce opposite results, yet are apparently mechanistically related. One possible explanation for these aberrations is the hypomethylation of the heterochromatic DNA sequences located at the pericentromeric regions. Hypomethylation of pericentric regions has been identified as an epigenetic mechanism for inducing tumour promoting chromosomal rearrangements of this type (Mitchell etal, 1996; Allshire, 1997; Karpen & Allshire, 1997). Chromosome 13 aberrations are currently the only chromosome aberration known to correlate with poor prognosis in MM (Tricot etal, 1995, 1997; Seong etal, 1998; Desikan etal, 2000; Konigsberg etal, 2000). We and colleagues have previously reported monosomy and deletion 13 in conventional karyotypes in MM, and have found even higher levels of del(13) and −13 using FISH techniques (Dao etal, 1994; Avet-Loiseau etal, 1999a, b; Shaughnessy etal, 2000). In this study, we again confirm chromosome 13 aberrations in over 50% of patients with complex karyotypes. However, with the complex scenario of aberrations found in MM, it seems probable that several other additional aberrations in combination with del(13) may eventually be related to poor prognosis. We therefore investigated whether any other recurring cytogenetic aberrations are strongly correlated with deletion or monosomy 13 and may be additional markers correlated with outcome. In a previous SKY study, we initially observed that all six patients with the t(14;16)(q32;q22) translocation also showed monosomy or deletion 13 (Sawyer etal, 1998a). Here, we found this same correlation in an additional eight patients, indicating that in every case where the t(14;16)(q32;q22) is found by SKY, del(13) or −13 is also found. This correlation, if confirmed by larger studies, may indicate that the t(14;16) is a possible candidate IgH translocation that occurs in combination with del(13) to confer poor prognosis. This study was supported in part by CA55819 from the National Cancer Institute. Allshire, R.C. (1997) Centromeres, checkpoints and chromatid cohesion. Current Opinion in Genetics and Development, 2, 264– 273.Grosbois, B. & Bataille, R. (1999a) Monosomy 13 is associated with the transition of monoclonal gammopathy of undetermined significance to multiple myeloma. Blood, 94, 2583– 2589.Grosbios, B. & Battaille, B. (1999b) 14q32 translocation and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. Cancer Research, 59, 4546– 4550.Kirby, S.L. & Kuehl, W.M. (1996) Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma. Proceedings of the National Academy of Sciences of the United States of America, 93, 13931– 13936.Cuesta, B. & Gullon, A. (1997) Cytogenetic analysis of 280 patients with multiple myeloma and related disorders: primary breakpoints and clinical correlations. Genes Chromosomes and Cancer, 18, 84– 93.DOI: Wiley Online LibraryKuehl, W.M. & Bergsagel, P.L. (1997) Frequent translocation of t(4;14)(p16.3;q32) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nature Genetics, 16, 260– 264.Reid, T. & Kuehl, W.M. (1998) Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma. Blood, 91, 4457– 4463.Barlogie, B. & Tricot, G. (1994) Deletion of the retinoblastoma gene in multiple myeloma. Leukemia, 8, 1280– 1294.Callanan, M. & Sotto, F. (1999) 1q unbalanced translocations in multiple myeloma involve breakpoints in the heterochromatin region and delineate distinct morphologic patterns: a cytogenetic/Fish and cytologic study. Blood, 94, 544a.Groffen J. & Grosveld, G. (1986) bcr rearrangment and translocaton of the c-abl oncogene in Philadelphia positive acute lymphoblastic leukemia. Blood, 68, 1369– 1375.Crowley, J. & Barlogie, B. (2000) Results of high dose therapy for1000 patient with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood, 95, 4008– 4010.Hicks, G.A. & Greip, P.R. (1995) The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia or amyloidosis. Blood, 66, 380– 390.Maiolo, A.T. & Neri, A. (1999) Detection of t(4;14) (p16.3;q32) chromosomal translocation in multiple myeloma bydouble-colour fluorescent in situ hybridization. Blood, 94, 724– 732.Lister, T.A. & Kearnery, L. (1994) Fluorescence in situ hybridization studies to characterize complete and partial monosomy 7 in myeloid disorders. Genes Chromosomes and Cancer, 10, 244– 249. Wiley Online LibraryBergsagel, P.L. & Anderson, K.C. (1998) Multiple myeloma: increasing evidence for a multistep transformation process. Blood, 91, 3– 21.Chaganti, R.S.K. & Dalla-Favera, R. (1997) Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma. Nature Genetics, 17, 226– 230. ISCN (1995) Guidelines for Cancer Cytogenetics, Supplement to an International System for Human Cytogenetic Nomenclature, (ed. by F. Mitelman). Karger, Basel.Alder, H. & Croce, C.M. (1999) The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors. Proceedings of the National Academy of Sciences of the United States of America, 96, 3928– 3933. Karpen, G.H. & Allshire, R.C. (1997) The case for epigenetic effects on centromere identity and function. Trends in Genetics, 12, 489– 496.Huber, H. & Drach, J. (2000) Predictive role of interphase cytogenetics for survival of patients with multiple myeloma. Journal of Clinical Oncology, 18, 804– 812.Morrison, H. & Kipling, D. (1996) Epigenetic control of mammalian centromere protein bindings: does DNA methylation have a role. Journal of Cell Science, 109, 2199– 2206.Oh, B.R. & Dahiya, R. (1999) Loss of two new loci on chromosome 8 (p23 and q12–13) in human prostate cancer. International Journal of Oncololgy, 14, 495– 500.Reid, T. & Chaganti, R.S.K. (1998) Karyotypic complexity of multiple myeloma defined by multicolour spectral karyotyping (SKY). Blood, 92, 1743– 1748.Jagannath, S. & Barlogie, B. (1995) Cytogenetic findings in 200 patients with multiple myeloma. Cancer Genetic and Cytogenetics, 82, 41– 49.Shaughnessy, J.D. & Barlogie, B. (1998a) Identification of new nonrandom translocations in multiple myeloma with multicolour spectral karyotyping. Blood, 92, 4269– 4278.Jagannath, S. & Barlogie, B. (1998b) Jumping translocations of chromosome 1q in multiple myeloma: evidence for a mechanism involving decondensation of pericentromeric heterochromatin. Blood, 91, 1732– 1741.Reid, T. (1996) Multicolor spectral karyotyping of human chromosomes. Science, 273, 494– 497.Epstein, J. & Barlogie, B. (2000) High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood, 96, 1505– 1511.Ballard, S.G. & Ward, D.C. (1996) Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics, 12, 368– 375.Pfranger, R. & Ponder, B.A. (1992) Cytogenetic analysis by chromosome painting using DOP-PCR amplified flow sorted chromosomes. Genes Chromosomes and Cancer, 4, 263– 267.Munshi, N. & Sawyer, J. (1995) Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities. Blood, 86, 4250– 4256.Munshi, N. & Barlogie, B. (1997) Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants. Journal of Clinical Oncology, 15, 2659– 2666.Rowley, J.D. & Reid, T. (1997) Hidden chromosome abnormalities in haematological malignancies detected by multicolour spectral karyotyping. Nature Genetics, 15, 406– 410.Ward, B. & Chrnevix-Trecnch, G. (1998) Frequent loss of heterozygosity and three critical regions on the short arm of chromosome 8 in ovarian adenocarcinomas. Oncogene, 17, 1185– 1188.Nakamura, Y. & Emi, M. (1999) Localization of a tumor suppressor gene associated with the progression of human breastcarcinoma with a 1-cm interval of 8p22-p23.1. Cancer, 85, 447– 452.DOI: Wiley Online LibraryThorgeirsson, S.S. & Popescu, N.C. (1998) Cloning characterization and chromosomal localization of a gene frequently deleted in human liver cancer (DCL-1) homologous to rat RhoGAP. Cancer Research, 58, 2196– 2199. 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