Abstract
Hyperhaploid multiple myeloma is a rare numerical aberration group defined by a range of 24-34 chromosomes, which is associated with a poor prognosis with a 5-year survival rate of 23%. Hyperhaploid patient samples (n=8) were sequenced and copy number and mutations identified. Samples had a median of 13 monosomies (range 12-14), which in general were those not associated with trisomies in hyperdiploid samples. The chromosomes traditionally trisomic in hyperdiploid myeloma were disomic in hyperhaploid myeloma with retention of heterodisomy. We examined the hyperhaploid samples for frequently mutated genes and found that 8/8 (100%) hyperhaploid samples had a mutation in TP53, exceeding the overall rate of mutation in newly diagnosed patients (5.5%), indicating an oncogenic dependency in this group. All samples with TP53 mutation also had monosomy of chromosome 17, indicating bi-allelic inactivation of TP53. As such, this high risk group is part of double-hit myeloma.
Highlights
Multiple myeloma (MM) is a plasma cell disorder characterized by multiple complex numerical and structural abnormalities [1]
We have previously shown that this group of patients is associated with a poor prognosis, with a 5-year survival rate of only 23% [2], and this was assumed to be linked to deletions of 17p and amplification of 1q in these samples
Hyperhaploidy results in monosomies of chromosomes 1 and 17, potentially giving reason to the poor prognosis associated with this group
Summary
Multiple myeloma (MM) is a plasma cell disorder characterized by multiple complex numerical and structural abnormalities [1]. Hyperdiploidy (47-57 chromosomes) is found in 50-60% of patients and is characterized by gains of whole chromosomes, consisting mostly of odd numbered chromosomes including 3, 5, 7, 9, 11, 15, 19, and 21. Hyperhaploidy is defined as a karyotype with 2434 chromosomes and is rare in MM [2, 3], but is seen in many cancer types, including acute lymphoblastic leukemia (ALL), myeloid leukemias, chondrosarcomas, and squamous cell carcinomas [4,5,6]. Hyperhaploidy in MM occurs with monosomy of many chromosomes, but those chromosomes associated with trisomies in hyperdiploidy remain disomic. In all cancers with hyperhaploidy, including MM, chromosome 18 is usually disomic, suggesting that disomy of chromosome 18 is required for a viable cell
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
