GSE141299 The effects of chromosomal copy number variations (CNV) on transcriptional programs at single cell resolution in multiple myeloma

Contributors : Ali M Shirayeh ; Rodger E TiedemannSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensChromosome copy number variations (CNV) are a near-universal feature of cancer however their specific effects on cellular function are poorly understood. Single-cell RNA sequencing (scRNA-seq) can reveal cellular gene expression however cannot directly link this to CNVs. Here we report scRNA-seq normalization methods that improve inter-cellular expression alignment, increasing the sensitivity of scRNA-seq for CNV detection. We additionally report sciCNV, a tool for inferring CNVs from scRNA-seq data. Together, these tools enable simultaneous profiling of DNA CNV and RNA within single cells. We apply these tools to multiple myeloma and examine the roles of pan cancer CNVs +8q and +1q. Cells with +8q23-24 upregulate MYC, MYC-target genes, mRNA translation, protein synthesis capacity and DEPTOR; and show reduced transcriptome size. Cells with +1q21-44 reconfigure translation to suppress unfolded protein stress and show increased proliferation, oxidative phosphorylation and MCL1. Overall, we report scRNA-seq methods that can reveal the function of CNVs in cancer.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Other Homo sapiens Source Type: research

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Personalized treatment is an attractive strategy that promises increased efficacy with reduced side effects in cancer. The feasibility of such an approach has been greatly boosted by next-generation sequencing (NGS) techniques, which can return detailed information on the genome and on the transcriptome of each patient's tumor, thus highlighting biomarkers of response or druggable targets that may differ from case to case. However, while the number of cancers sequenced is growing exponentially, much fewer cases are amenable to a molecularly-guided treatment outside of clinical trials to date. In multiple myeloma, genomic a...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conditions:   Chronic Lymphocytic Leukemia;   Chronic Myelogenous Leukemia, BCR-ABL1 Positive;   Plasma Cell Myeloma Interventions:   Behavioral: The DISCO App;   Behavioral: Usual Care Sponsor:   Barbara Ann Karmanos Cancer Institute Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 22 February 2020Source: International Journal of PharmaceuticsAuthor(s): Sarita Rani, Rakesh K. Sahoo, Kartik T. Nakhate, Ajazuddin, Umesh GuptaAbstractBortezomib (BTZ) is a proteasome inhibitor as approved by US FDA for the treatment of multiple myeloma. It exhibits significant anti-cancer properties including against solid tumors; but lacks aqueous solubility, chemical stability which hinders its successful formulation development. The present study is an attempt to deliver BTZ using N-(2-hydroxypropyl) methacrylamide (HPMA) based copolymeric conjugates and biotinylated PNPs in an effec...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 19 February 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Vasu Saini, Aditi Dhir, Ariana W. Rudnick, Joshua Lukas, Karlo J. Lizarraga, Jason Margolesky, Deborah O. Heros, James E. HoffmanAbstractParaneoplastic neurologic syndromes are rare but well described presentation of certain malignancies in both children and adults. Cerebellar dysfunction is a common paraneoplastic presentation and has been previously reported in association with small cell lung cancer, breast cancers, ovarian tumors, renal cell carcinoma, follicular lymphoma, and Hodgkin’s lymphoma. There are ...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
(American Association for Cancer Research) The loss of one copy of the miR15a/miR16-1 gene cluster promoted initiation and progression of multiple myeloma in mice.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Abstract Dickkopf-1 (DKK1), broadly expressed by tumor cells from human multiple myeloma (MM) and other cancers but absent from most normal tissues, may be an ideal target for immunotherapy. Our previous studies have shown that DKK1 (peptide)-specific cytotoxic T lymphocytes can effectively lyse primary MM cells in vitro. To develop DKK1-based vaccines that can be easily and inexpensively made and used by all patients, we identified a DKK1 long peptide (LP), DKK13-76-LP, that contains 74 amino acids and epitopes that can potentially bind to all major MHC class I and II molecules. Using HLA-A*0201- and HLA-DR*4-tra...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Abstract Disruption of the normal splicing patterns of RNA is a major factor in the pathogenesis of a number of diseases. Increasingly research has shown the strong influence that splicing patterns can have on cancer progression. Multiple Myeloma is a molecularly heterogeneous disease classified by the presence of key translocations, gene expression profiles and mutations but the splicing patterns in MM remains largely unexplored. We take a multifaceted approach to define the extent and impact of alternative splicing in MM. We look at the spliceosome component, SF3B1, with hotspot mutations (K700E and K666T/Q) sho...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
çoise Kraeber-Bodere Multiple myeloma (MM) is always preceded by an initial monoclonal gammopathy of undetermined significance (MGUS) that then develops into asymptomatic or smoldering multiple myeloma (SMM), which constitutes an intermediate clinical stage between MGUS and MM. According to a recent study, risk factors for faster MGUS to MM progression include an M protein of 1.5 g/dL or more and an abnormal free light chain ratio in patients with non-IgM MGUS. Therefore, the International Myeloma Working Group (IMWG) decided to recommend whole-body computed tomography (WBCT) for patients with high-risk MGUS in ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Paraneoplastic neurologic syndromes are rare but well described presentation of certain malignancies in both children and adults. Cerebellar dysfunction is a common paraneoplastic presentation and has been previously reported in association with small cell lung cancer, breast cancers, ovarian tumors, renal cell carcinoma, follicular lymphoma, and Hodgkin ’s lymphoma. There are only a handful of case reports with the association of paraneoplastic neurologic presentation with Non-Hodgkin lymphoma including Diffuse Large B-cell Lymphoma (DLBCL).
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Case Report Source Type: research
Blood Cancer Journal, Published online: 17 February 2020; doi:10.1038/s41408-020-0284-7Dissecting racial disparities in multiple myeloma
Source: Blood Cancer Journal - Category: Hematology Authors: Source Type: research
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