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Updated: Nov 6, 2025
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome
Katia Todoerti1, Domenica Ronchetti2, Vanessa Favasuli2
1Hematology, Fondazione Cà Granda IRCCS Policlinico, Milan, Italy; Department of Oncology and Hemato-oncology, University of Milan.
Abstract:
DIS3 gene mutations occur in roughly 10% of patients with multiple myeloma (MM); furthermore, DIS3 expression can be affected by monosomy 13 and del(13q), which occur in approximately 40% of MM cases. Despite several reports on the prevalence of DIS3 mutations, their contribution to the pathobiology of MM remains largely unknown. We took advantage of the large public CoMMpass dataset to investigate the spectrum of DIS3 mutations in MM and its impact on the transcriptome and clinical outcome. We found that the clinical relevance of DIS3 mutations strictly depended on the co-occurrence of del(13q). In particular, bi-allelic DIS3 lesions significantly affected progression-free survival, independently of other predictors of poor clinical outcome, while mono-allelic events mostly affected overall survival. As expected, DIS3 mutations affect the MM transcriptome involving cellular processes and signaling pathways associated with RNA metabolism, and the deregulation of a large number of long non-coding RNA, among which we identified five distinct transcripts as independent predictors of poorer overall survival and nine of worse progression-free survival, with two (AC015982.2 and AL445228.3) predicting both unfavorable outcomes. These findings strongly prompt further studies investigating the relevance of these long non-coding RNA in MM.
Insights
DIS3 gene mutations impact multiple myeloma (MM) progression, especially when combined with del(13q). Specific long non-coding RNAs linked to DIS3 alterations predict survival outcomes in MM patients.
Area of Science:
- Hematology
- Genetics
- Oncology
Background:
- DIS3 gene mutations are found in about 10% of multiple myeloma (MM) cases.
- DIS3 expression is also impacted by chromosomal abnormalities like monosomy 13 and del(13q) in approximately 40% of MM patients.
- The role of DIS3 mutations in MM pathobiology is not well understood.
Purpose of the Study:
- To investigate the range of DIS3 mutations in MM using the CoMMpass dataset.
- To analyze the impact of DIS3 mutations on the MM transcriptome.
- To determine the effect of DIS3 mutations on clinical outcomes in MM.
Main Methods:
- Utilized the CoMMpass dataset, a large public resource for multiple myeloma research.
- Analyzed the spectrum of DIS3 mutations within the dataset.
- Correlated DIS3 mutations with transcriptome data and clinical outcomes, including progression-free and overall survival.
Main Results:
- The clinical significance of DIS3 mutations is dependent on the co-occurrence of del(13q).
- Bi-allelic DIS3 lesions significantly worsen progression-free survival, independent of other poor prognostic factors.
- Mono-allelic DIS3 events primarily impact overall survival.
- DIS3 mutations alter the MM transcriptome, affecting RNA metabolism and deregulating long non-coding RNAs (lncRNAs).
- Identified specific lncRNAs (e.g., AC015982.2, AL445228.3) as independent predictors of poor overall and progression-free survival.
Conclusions:
- DIS3 mutations, particularly in conjunction with del(13q), are significant prognostic factors in multiple myeloma.
- Transcriptome alterations driven by DIS3 mutations involve lncRNA deregulation.
- Identified lncRNAs warrant further investigation for their therapeutic potential in multiple myeloma.
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