Deletion Of Chromosome 13q

Deletion of chromosome 13q is the most common recurrent chromosomal abnormality in myeloma. It is detected in 15-20% of myeloma by CC,21 50% of cases by interphase FISH in newly diagnosed myeloma patients,22 and 30-45% of cases of MGUS.23'24 The prognostic significance of loss of 13q identified by FISH alone has been the subject of considerable debate. Several studies based on molecular cytogenetics have shown that this abnormality is strongly associated with an unfavorable prognosis.2325-32 It correlates with advanced stage, elevated ^-microglobulin, increased percentage of plasma cells, increased proliferative rate, and reduced overall survival. However, a multivariate analysis identified t(4;14), t(14;16), and the deletion of 17p13 as independent predictors of survival, while loss of 13q was found to be of only borderline significance.33

Chromosome 13 abnormalities are frequently associated with other chromosomal aberrations. It was observed that, while all patients carrying translocations involving the IgH locus, such as t(4;14) and t(14;16), also had loss of chromosome 13, del(13q), the reverse was not true.24 34 This suggests the possibility that del(13q) occurred before the IgH translocation events, perhaps as an early oncogenic change. A role for monosomy 13 in the transformation of MGUS to myeloma has also been proposed, supported by a higher incidence of monosomy 13 in myeloma cases

Deletion Chromosome Myeloma

Figure 81.6 Multiple myeloma karyotype: Top panel shows G-banded karyotype with extra copies of chromosomes 5, 7, 9, 15, and 19, loss of the Y chromosome, monosomy 13, and complex unbalanced rearrangements involving chromosomes 16, 17, and 20. The complex der(16) and cryptic t(8;21) were identified only on M-FISH (shown in the bottom panel). The t(8;21) breakpoint on 8q is at the site of the MYC gene

Figure 81.6 Multiple myeloma karyotype: Top panel shows G-banded karyotype with extra copies of chromosomes 5, 7, 9, 15, and 19, loss of the Y chromosome, monosomy 13, and complex unbalanced rearrangements involving chromosomes 16, 17, and 20. The complex der(16) and cryptic t(8;21) were identified only on M-FISH (shown in the bottom panel). The t(8;21) breakpoint on 8q is at the site of the MYC gene with preexisting MGUS (70%) compared with those cases without such a history (31%).35 Moreover, in 18 asymptomatic, untreated patients with MGUS studied serially with both CC and FISH over 6-72 months (median 30 months), del(13q14) was identified in 5 patients over the course of the study, but in only 1 of these patients was the del(13q) detected at diagnosis. All five patients proceeded to develop multiple myeloma (MM) 6-12 months after 13q deletion identification, whereas only 2/13 patients without evidence of del(13q) transformed to MM.

The majority of chromosome 13 abnormalities (92%) are complete monosomies,22 with the remaining being partial deletions.

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