Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma

Abstract

In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (D13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n ¼ 794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if D13, p53 deletion or t(4;14) was present, but only D13 remained significant on multivariate analysis. Patients with D13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with D13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable D13 disappeared; their outcome matched that of patients with no detectable D13 (P ¼ 0.115). Addition of ploidy status to iFISH-D13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH D13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with D13. We conclude that D13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of D13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.

Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma

“…25 Cases were classified according to the following abnormalities: the presence of any IgH translocation (including unknown partner chromosome); the common translocations t(4;14), t(6;14), t(11;14), t(14;16), t (14;20), and t(8;14); deletions of 13q14, 14q32, 16q23, and 17p13; and hyperdiploid status using the iFISH (interphase fluorescence in situ hybridization) ploidy classification previously described. 25 Deletion of 14q was deduced from loss of the whole IgH probe or loss of the proximal signal where there was a split, and del(16q) was deduced from loss of the MAF part of the Abbott IgH/MAF probe combination. When scoring fusion probes, the number of copies of each probe was carefully noted as were the presence or absence and number of fusions.…”

“…The correlations between other FISH abnormalities and cytogenetic abnormalities have been reported previously. 25 Del(16q) was significantly associated with deletion of 13q (P ϭ .009), deletion of the IgH probe on 14q (P Ͻ .001), deletion of p53 on 17p (P Ͻ .001), and with nonhyperdiploid status (P ϭ .043; Table 1). …”

In pursuit of the allo-immune response in multiple myeloma: where do we go from here?

“…The presence of chromosome 13 deletion by conventional karyotyping and the t(4;14), t(14;16), t (14;20), and deletion of 17p by FISH have been shown to confer an adverse outcome. [13][14][15] Gene expression profiling has also been used to define patients who are at 'high risk'. 16 However, the routine clinical use of these tests in selecting therapy for individual patients remains unproven.…”

Spotlight review series on multiple myeloma

“…The prognosis and response to therapy of myeloma vary greatly based on baseline cytogenetic abnormalities. [22][23][24][25][26][27][28] In fact, it is likely that in the future treatments will be delivered in a more individualized manner based on underlying chromosomal and gene-expression characteristics. 29 To highlight and critically evaluate recent advances in the biology and treatment of myeloma, we published a special spotlight series of 14 comprehensive review articles in Leukemia.…”