Hyperhaploidy is a novel high-risk cytogenetic subgroup in multiple myeloma.
Hyperhaploid clones (24-34 chromosomes) were identified in 33 patients with multiple myeloma (MM), demonstrating a novel numerical cytogenetic subgroup. Strikingly, all hyperhaploid karyotypes were found to harbor monosomy 17p, the single most important risk stratification lesion in MM. A catastrophic loss of nearly a haploid set of chromosomes results in disomies of chromosomes 3, 5, 7, 9, 11, 15, 18, 19 and 21, the same basic set of odd-numbered chromosomes found in trisomy in hyperdiploid myeloma. All other autosomes are found in monosomy, resulting in additional clinically relevant monosomies of 1p, 6q, 13q and 16q. Hypotriploid subclones (58-68 chromosomes) were also identified in 11 of the 33 patients and represent a duplication of the hyperhaploid clone. Analysis of clones utilizing interphase fluorescence in situ hybridization (iFISH), metaphase FISH and spectral karyotyping identified either monosomy 17 or del17p in all patients. Amplification of 1q21 was identified in eight patients, demonstrating an additional high-risk marker. Importantly, our findings indicate that current iFISH strategies may be uninformative or ambiguous in the detection of these clones, suggesting this patient subgroup maybe underreported. Overall survival for patients with hyperhaploid clones was poor, with a 5-year survival rate of 23.1%. These findings identify a distinct numerical subgroup with cytogenetically defined high-risk disease.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
J R
JR
Sawyer
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
E
E
Tian
Signal Genetics Inc., Carlsbad, CA, USA.
J D
JD
Shaughnessy
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
J
J
Epstein
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
C M
CM
Swanson
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
C
C
Stangeby
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
C L
CL
Hale
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
L
L
Parr
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
M
M
Lynn
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
G
G
Sammartino
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
J L
JL
Lukacs
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
C
C
Stein
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
C
C
Bailey
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
M
M
Zangari
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
F E
FE
Davies
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
F
F
Van Rhee
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
B
B
Barlogie
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
G J
GJ
Morgan
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D003582:Cytogenetics; D005260:Female; D006238:Haploidy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D011123:Polyploidy; D011379:Prognosis; D016016:Proportional Hazards Models
D015415:Biomarkers
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