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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1505-1511
NEOPLASIA
High incidence of chromosome 13 deletion in multiple
myeloma detected by multiprobe interphase FISH
John Shaughnessy Jr,
Erming Tian,
Jeffrey Sawyer,
Klaus Bumm,
Reid Landes,
Ashraf Badros,
Christopher Morris,
Guido Tricot,
Joshua Epstein, and
Bart Barlogie
From the Myeloma and Transplantation Research Center,
Division of Biometry, University of Arkansas for Medical Sciences and
Arkansas Cancer Research Center, Little Rock, AR
Multiple myeloma (MM) is a hypoproliferative
malignancy yielding informative karyotypes in no more than 30% of
newly diagnosed cases. Although cytogenetic and molecular deletion of
chromosome 13 is associated with poor prognosis, a MM tumor suppressor
gene (TSG) has not been identified. To localize a minimal deleted
region of chromosome 13, clonotypic plasma cells from 50 consecutive patients with MM were subjected to interphase fluorescence in situ
hybridization (FISH) analysis using a panel of 11 probes spanning the
entire long arm of chromosome 13. Whereas chromosome 13 abnormalities
were absent in plasma cells from 25 normal donors, 86% of patients
with MM demonstrated such aberrations. Heterogeneity, both in deletion
frequency and extent, was confirmed by simultaneous FISH with 2 chromosome 13 probes. Deletion hot spots were noted at D13S272 (70%)
and D13S31 (64%), 2 unlinked loci at 13q14. Homozygous deletions at
these loci occurred in 12% (simultaneously in 8%) of the cases.
Molecular deletions were found in all 14 patients with morphologic
deletions, in 21 of 24 with uninformative karyotypes, and 8 of 12 patients with karyotype abnormalities lacking chromosome 13 deletion.
Homozygous deletion of any marker was noted in 4% with low and in 36%
with higher plasma cell labeling index greater than 0.4%
(P = .01). The absence of increasing deletion
incidence and extent with therapy duration suggests that the observed
lesions are not induced by treatment. The high incidence and extent of chromosome 13 deletions require the correlation of specific deletion(s) with poor prognosis. These analyses will provide valuable guidance toward cloning of an MM-TSG.

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