A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS.
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.
Chng
Wee Joo
WJ
Mayo Clinic Scottsdale, Comprehensive Cancer Center and Division of Hematology and Onocology, Scottsdale, AZ 85259, USA.
Van Wier
Scott A
SA
Ahmann
Gregory J
GJ
Winkler
Jerry M
JM
Jalal
Syed M
SM
Bergsagel
Peter Leif
PL
Chesi
Marta
M
Trendle
Mike C
MC
Oken
Martin M
MM
Blood
Emily
E
Henderson
Kim
K
Santana-Dávila
Rafael
R
Kyle
Robert A
RA
Gertz
Morie A
MA
Lacy
Martha Q
MQ
Dispenzieri
Angela
A
Greipp
Philip R
PR
Fonseca
Rafael
R
D015331:Cohort Studies; D004171:Diploidy; D005434:Flow Cytometry / Q000592:standards; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000592:standards*; D009101:Multiple Myeloma / Q000235:genetics; D010265:Paraproteinemias / Q000175:diagnosis* / Q000235:genetics*; D012680:Sensitivity and Specificity; D014314:Trisomy