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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2156-2161.
Prepublished online as a Blood First Edition Paper on May 26, 2005; DOI 10.1182/blood-2005-02-0761.
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NEOPLASIA
A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS
Wee Joo Chng,
Scott A. Van Wier,
Gregory J. Ahmann,
Jerry M. Winkler,
Syed M. Jalal,
Peter Leif Bergsagel,
Marta Chesi,
Mike C. Trendle,
Martin M. Oken,
Emily Blood,
Kim Henderson,
Rafael Santana-Dávila,
Robert A. Kyle,
Morie A. Gertz,
Martha Q. Lacy,
Angela Dispenzieri,
Philip R. Greipp, and
Rafael Fonseca
From the Mayo Clinic Scottsdale, Comprehensive Cancer Center and Division of Hematology and Onocology, Scottsdale, AZ; the Department of Haematology-oncology, National University Hospital, Singapore; the Mayo Clinic Rochester, Division of Hematology, and the Department of Laboratory Medicine and Pathology, Rochester, MN; Missouri Cancer Associates, Columbia, MO; North Memorial Cancer Center, Robbinsdale, MN; the Eastern Cooperative Oncology Group (ECOG) Statistical Center, and the Dana Farber Cancer Institute, Boston, MA.
Two major genetic categories of multiple myeloma (MM) exist. Hyperdiploid MM (48 to 74 chromosomes, median 53 chromosomes) is associated with trisomies especially of chromosomes 3, 7, 9, 11, 15, and 19, whereas the nonhyperdiploid (< 48 chromosomes or more than 74 chromosomes) MM is associated with primary translocations such as t(11;14), t(4;14), and t(14;16). Whether this dichotomy exists in monoclonal gammopathy of undetermined significance (MGUS) is uncertain due to limitations of current methods in the study of ploidy. This is especially true in MGUS where the number of clonal plasma cells is small. In this study, we derived a fluorescent in situ hybridization (FISH)-based trisomy index from pooled cytogenetic data (karyotype analysis) from 2 large cohorts of patients with MM with abnormal karyotype, and then validated it in 2 independent cohorts of patients who had known ploidy status either by karyotyping or DNA content measurement using flow cytometry. Using the criteria of 2 or more trisomies from a 3-chromosome combination, hyperdiploid myeloma can be detected with high specificity. Applying this index on 28 patients with smoldering multiple myeloma (SMM) or MGUS (11 SMM, 17 MGUS) who had normal karyotype, 11 cases of hyperdiploid SMM/MGUS were detected. This percentage (40%) is remarkably similar to the percentage of hyperdiploid MM reported in the literature, suggesting that hyperdiploid MM may originate early during disease evolution. (Blood. 2005;106: 2156-2161)
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