Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma.

ABSTRACT: Chromothripsis is detectable in 20-30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study we interrogate 752 NDMM patients using whole genome sequencing (WGS) to investigate the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC = 0.90) and can be used identify its adverse prognostic impact. The ability of CN signatures to predict the presence of chromothripsis is confirmed in a validation series of WGS comprised of 235 hematological cancers (AUC = 0.97) and an independent series of 34 NDMM (AUC = 0.87). We show that CN signatures can also be derived from whole exome data (WES) and using 677 cases from the same series of NDMM, we are able to predict both the presence of chromothripsis (AUC = 0.82) and its adverse prognostic impact. CN signatures constitute a flexible tool to identify the presence of chromothripsis and is applicable to WES and WGS data.

SUBMITTER: Maclachlan KH

PROVIDER: S-EPMC8397708 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Chromothripsis identifies a rare and aggressive entity among newly diagnosed multiple myeloma patients.

Project description:Multiple myeloma (MM) develops from a premalignant plasma cell proliferative disorder, and with time can progress to a more aggressive disease in extramedullary locations. The gradually clinical evolution is supported by clonal expansion of cells that acquire genetic lesions over years. This model of cancer evolution based on ongoing genomic instability mechanism may apply to development of most MM cases. However, in a small fraction of newly diagnosed MM who relapse quickly and finally die within 2 years, the gradual model appears to be untenable. Analysis of high resolution copy number profiles obtained using single nucleotide polymorphism array data from 764 newly diagnosed MM identified large numbers of genomic rearrangements with the hallmarks of chromothripsis in 1.3% of samples. Moreover, this catastrophic event confers a poor outcome. Because chromothripsis appears to occur in a single crisis, our results suggest that high-risk MM patients use this novel way of cancer evolution.

| S-EPMC3142904 | biostudies-literature

Chromothripsis identifies a rare and aggressive entity among newly diagnosed multiple myeloma patients

Project description:Comment on published article "Massive genomic rearrangement acquired in a single catastrophic event during cancer development." by Stephens, P.J., Greenman, C.D., Beiyuan, F., Yang, F., Bignell, G.R., Mudie, L.J., Pleasance, E.D., Lau, K.W., Beare, D., Stebbings, L.A., et al. (2011). Cell 144, 27-40. [PMID: 21215367]

2011-06-06 | GSE27560 | GEO

Chromothripsis identifies a rare and aggressive entity among newly diagnosed multiple myeloma patients

2011-06-06 | E-GEOD-27560 | biostudies-arrayexpress

Hematopoietic score predicts outcomes in newly diagnosed multiple myeloma patients.

Project description:Risk stratification of multiple myeloma (MM) at diagnosis is critical. We examined the ability of hematopoietic indices including mean corpuscular volume (MCV), hemoglobin (Hgb), and platelet (Plt) to predict outcomes. This was a retrospective study of patients treated at Mayo Clinic between January 2004 and April 2018. We incorporated three variables (Hgb?<?10 g/dL, Plt?<?150?×?109 /L, and MCV?>?96?fL), assigning a score of 1 to each. We identified 1540 newly diagnosed MM patients, of whom 707 (46%) had a score of 0, 513 (33%) had a score of 1, 260 (17%) had a score of 2, and 60 (4%) had a score of 3. The score risk stratified patients into four groups with differing survivals. The median PFS was 32.3 months for score 0, 24.8 months for score 1, 21.7 months for score 2, and 18.3 months for score 3, for P <?.001. The median OS was 80.7 months for score 0, 59.9 months for score 1, 51.7 months for score 2, and 31.3 months for score 3, P <?.0001. Predictors of OS on the multivariable analysis were age???65 (HR, 1.93; P <?.0001), R-ISS stage (1-2 vs 3) (HR, 0.48; P <?.0001), and hematopoietic score (0-2 vs 3) (HR, 0.51; P =?.006). A hematopoietic score can predict survival in newly diagnosed myeloma patients.

| S-EPMC7377299 | biostudies-literature

Prognostic value of integrated cytogenetic, somatic variation, and copy number variation analyses in Korean patients with newly diagnosed multiple myeloma.

Project description:BackgroundTo investigate the prognostic value of gene variants and copy number variations (CNVs) in patients with newly diagnosed multiple myeloma (NDMM), an integrative genomic analysis was performed.MethodsSixty-seven patients with NDMM exhibiting more than 60% plasma cells in the bone marrow aspirate were enrolled in the study. Whole-exome sequencing was conducted on bone marrow nucleated cells. Mutation and CNV analyses were performed using the CNVkit and Nexus Copy Number software. In addition, karyotype and fluorescent in situ hybridization were utilized for the integrated analysis.ResultsEighty-three driver gene mutations were detected in 63 patients with NDMM. The median number of mutations per patient was 2.0 (95% confidence interval [CI] = 2.0-3.0, range = 0-8). MAML2 and BHLHE41 mutations were associated with decreased survival. CNVs were detected in 56 patients (72.7%; 56/67). The median number of CNVs per patient was 6.0 (95% CI = 5.7-7.0; range = 0-16). Among the CNVs, 1q gain, 6p gain, 6q loss, 8p loss, and 13q loss were associated with decreased survival. Additionally, 1q gain and 6p gain were independent adverse prognostic factors. Increased numbers of CNVs and driver gene mutations were associated with poor clinical outcomes. Cluster analysis revealed that patients with the highest number of driver mutations along with 1q gain, 6p gain, and 13q loss exhibited the poorest prognosis.ConclusionsIn addition to the known prognostic factors, the integrated analysis of genetic variations and CNVs could contribute to prognostic stratification of patients with NDMM.

| S-EPMC7864461 | biostudies-literature

Optimizing outcomes for patients with newly diagnosed multiple myeloma eligible for transplantation.

Project description:High-dose therapy with autologous stem cell transplantation (HDT-ASCT) has been considered to be the standard frontline treatment for younger, fit patients with multiple myeloma (MM) since the 1990s. Efforts continue to optimize the use of HDT-ASCT with the aim of improving outcomes. One strategy has been the incorporation of novel agents (thalidomide, lenalidomide and bortezomib) in the pre-transplantation setting as an induction therapy or in the post-transplantation setting as a consolidation or maintenance therapy. Given their high response rates, three-drug induction therapy regimens (for example, bortezomib-thalidomide-dexamethasone, lenalidomide-bortezomib-dexamethasone and cyclophosphamide-bortezomib-dexamethasone) are now the standard of care. Thalidomide and bortezomib are well suited for consolidation therapy, and regimens using these agents can improve the depth of response following HDT-ASCT. Lenalidomide is particularly well suited for long-term maintenance therapy following HDT-ASCT, and initial results are promising and have shown improvements in disease outcomes such as progression-free survival and overall survival in some cases, although a low incidence of second primary malignancies have been observed. Further studies are needed to determine the optimal regimen and duration of induction therapy, the impact of maintenance on overall survival and the safety of long-term treatment. Many of the studies currently underway in MM will help address these aspects.

| S-EPMC4851188 | biostudies-literature

Expression data of newly diagnosed multiple myeloma and extramedullary myeloma

Project description:Despite the development of novel therapeutic agents, multiple myeloma (MM) remains incurable, owing mainly to inevitable relapse in almost all patients. Some relapses occur as extramedullary disease (EMD), which is rare but is the most aggressive event in MM patients. Extramedullary myeloma (EMM) has extraordinary heterogeneous biological and clinical features. Previous studies have shown that expression levels of LncRNAs and mRNAs in different stages of MM are different. This study analyzes the expression levels of LncRNAs and mRNAs in primary plasma cells (PCs) from MM and EMM patients.

2023-03-01 | GSE147841 | GEO

Daratumumab in untreated newly diagnosed multiple myeloma.

Project description:The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown clinical efficacy in relapsed/refractory multiple myeloma both as monotherapy and in combination with other drugs, including novel agents. More recently, promising results have been reported in patients with untreated newly diagnosed multiple myeloma (NDMM). Clinical trials thus far have shown enhanced efficacy and tolerability of several daratumumab-based combinations in both transplant ineligible and eligible patients, without compromising transplant ability. However, benefit in high-risk subpopulations is still unclear. A subcutaneous formulation of daratumumab has been introduced to decrease the risk of infusion reactions, with preliminary results showing non-inferior efficacy. The antimyeloma activity of daratumumab is achieved through multiple mechanisms including direct, Fc-dependent, and immunomodulatory mechanisms. Enhanced efficacy of daratumumab in combination with immunomodulatory drugs and proteasome inhibitors is supported by preclinical data showing synergism. This review will focus on the role of daratumumab in untreated NDMM patients, highlighting the results of major clinical trials, and listing ongoing trials that are evaluating various daratumumab-based combinations in this setting.

| S-EPMC6928545 | biostudies-literature

Hydroxymethylation in newly diagnosed Multiple Myeloma

Project description:DNA Hydroxymethylation is Associated with Disease Severity and Persists at Enhancers of Oncogenic Regions in Multiple Myeloma

| PRJEB32800 | ENA

The outcomes of newly diagnosed elderly multiple myeloma patients treated at a single U.S. institution.

Project description:Improvements in the outcomes of elderly multiple myeloma (MM) patients have lagged behind those of transplant-eligible patients, likely due in part to the use of less efficacious melphalan-containing regimens. To date, there are very limited data for the outcomes of elderly MM patients in the United States (US), particularly for novel agent-containing triplet regimens. In this retrospective study at a single U.S. institution, the outcomes of 117 consecutive newly diagnosed, symptomatic MM patients over the age of 70 were evaluated. The median age was 75 years (range 70-95) with significant baseline comorbidities including 36% cardiac and 20% renal (CrCl < 30 mL/min). The median follow-up was 43 months and the median number of lines of therapy during the study period was 2 (1-7). Eighty-six patients (83%) received non-melphalan doublet, triplet, or quadruplet initial therapy, most with significant planned dose attenuations. For those treated with dose-attenuated RVD (n = 34), the outcomes were particularly impressive with overall response rate (ORR), complete remission and very good partial remission (CR + VGPR), and progression-free survival (PFS) of 94%, 65%, and 36 months, respectively, and overall survival (OS) not reached. The PFS with RVD was significantly greater than that of all other regimens (P = 0.030), including RD.

| S-EPMC4799960 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data