Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma

Domenica Ronchetti, Luca Agnelli, Elisa Taiana, Serena Galletti, Martina Manzoni, Katia Todoerti, Pellegrino Musto, Francesco Strozzi, Antonino Neri

Research output: Contribution to journalArticle

Abstract

Although many efforts have recently contributed to improve our knowledge of molecular pathogenesis of multiple myeloma (MM), the role and significance of long non-coding RNAs (lncRNAs) in plasma cells (PC) malignancies remains virtually absent. To this aim, we developed a custom annotation pipeline of microarray data investigating lncRNA expression in PCs from 20 monoclonal gammopathies of undetermined significance, 33 smoldering MM, 170 MM, and 36 extra-medullary MMs/plasma cell leukemia patients, and 9 healthy donors. Our study identified 31 lncRNAs deregulated in tumor samples compared to normal controls; among these, the upregulation of MALAT1 appeared associated in MM patients with molecular pathways involving cell cycle regulation, p53-mediated DNA damage response, and mRNA maturation processes. Furthermore, we found 21 lncRNAs whose expression were progressively deregulated trough the more aggressive stages of PC dyscrasia, suggesting a possible role in the progression of the disease. Finally, in the context of molecular heterogeneity of MM, we identified a transcriptional fingerprint in hyperdiploid patients, characterized by the upregulation of lncRNAs/pseudogenes related to ribosomal protein genes, known to be upregulated in this molecular group. Overall, the data provides an important resource for future studies on the functions of lncRNAs in the pathology.

Original languageEnglish
Pages (from-to)14814-14830
Number of pages17
JournalOncotarget
Volume7
Issue number12
DOIs
Publication statusPublished - Mar 22 2016

Fingerprint

Long Noncoding RNA
Dermatoglyphics
Multiple Myeloma
Up-Regulation
Plasma Cell Leukemia
Monoclonal Gammopathy of Undetermined Significance
Pseudogenes
Paraproteinemias
Polyploidy
Ribosomal Proteins
Plasma Cells
DNA Damage
Disease Progression
Neoplasms
Cell Cycle
Tissue Donors
Pathology
Messenger RNA
Genes

Keywords

  • Expression profiling
  • LncRNA
  • MALAT1
  • Multiple myeloma
  • Plasma cell dyscrasia

ASJC Scopus subject areas

  • Oncology

Cite this

Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma. / Ronchetti, Domenica; Agnelli, Luca; Taiana, Elisa; Galletti, Serena; Manzoni, Martina; Todoerti, Katia; Musto, Pellegrino; Strozzi, Francesco; Neri, Antonino.

In: Oncotarget, Vol. 7, No. 12, 22.03.2016, p. 14814-14830.

Research output: Contribution to journalArticle

Ronchetti, D, Agnelli, L, Taiana, E, Galletti, S, Manzoni, M, Todoerti, K, Musto, P, Strozzi, F & Neri, A 2016, 'Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma', Oncotarget, vol. 7, no. 12, pp. 14814-14830. https://doi.org/10.18632/oncotarget.7442
Ronchetti, Domenica ; Agnelli, Luca ; Taiana, Elisa ; Galletti, Serena ; Manzoni, Martina ; Todoerti, Katia ; Musto, Pellegrino ; Strozzi, Francesco ; Neri, Antonino. / Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma. In: Oncotarget. 2016 ; Vol. 7, No. 12. pp. 14814-14830.
@article{e5bcd923338847fa950ac9405fdebf0c,
title = "Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma",
abstract = "Although many efforts have recently contributed to improve our knowledge of molecular pathogenesis of multiple myeloma (MM), the role and significance of long non-coding RNAs (lncRNAs) in plasma cells (PC) malignancies remains virtually absent. To this aim, we developed a custom annotation pipeline of microarray data investigating lncRNA expression in PCs from 20 monoclonal gammopathies of undetermined significance, 33 smoldering MM, 170 MM, and 36 extra-medullary MMs/plasma cell leukemia patients, and 9 healthy donors. Our study identified 31 lncRNAs deregulated in tumor samples compared to normal controls; among these, the upregulation of MALAT1 appeared associated in MM patients with molecular pathways involving cell cycle regulation, p53-mediated DNA damage response, and mRNA maturation processes. Furthermore, we found 21 lncRNAs whose expression were progressively deregulated trough the more aggressive stages of PC dyscrasia, suggesting a possible role in the progression of the disease. Finally, in the context of molecular heterogeneity of MM, we identified a transcriptional fingerprint in hyperdiploid patients, characterized by the upregulation of lncRNAs/pseudogenes related to ribosomal protein genes, known to be upregulated in this molecular group. Overall, the data provides an important resource for future studies on the functions of lncRNAs in the pathology.",
keywords = "Expression profiling, LncRNA, MALAT1, Multiple myeloma, Plasma cell dyscrasia",
author = "Domenica Ronchetti and Luca Agnelli and Elisa Taiana and Serena Galletti and Martina Manzoni and Katia Todoerti and Pellegrino Musto and Francesco Strozzi and Antonino Neri",
year = "2016",
month = "3",
day = "22",
doi = "10.18632/oncotarget.7442",
language = "English",
volume = "7",
pages = "14814--14830",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "12",

}

TY - JOUR

T1 - Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma

AU - Ronchetti, Domenica

AU - Agnelli, Luca

AU - Taiana, Elisa

AU - Galletti, Serena

AU - Manzoni, Martina

AU - Todoerti, Katia

AU - Musto, Pellegrino

AU - Strozzi, Francesco

AU - Neri, Antonino

PY - 2016/3/22

Y1 - 2016/3/22

N2 - Although many efforts have recently contributed to improve our knowledge of molecular pathogenesis of multiple myeloma (MM), the role and significance of long non-coding RNAs (lncRNAs) in plasma cells (PC) malignancies remains virtually absent. To this aim, we developed a custom annotation pipeline of microarray data investigating lncRNA expression in PCs from 20 monoclonal gammopathies of undetermined significance, 33 smoldering MM, 170 MM, and 36 extra-medullary MMs/plasma cell leukemia patients, and 9 healthy donors. Our study identified 31 lncRNAs deregulated in tumor samples compared to normal controls; among these, the upregulation of MALAT1 appeared associated in MM patients with molecular pathways involving cell cycle regulation, p53-mediated DNA damage response, and mRNA maturation processes. Furthermore, we found 21 lncRNAs whose expression were progressively deregulated trough the more aggressive stages of PC dyscrasia, suggesting a possible role in the progression of the disease. Finally, in the context of molecular heterogeneity of MM, we identified a transcriptional fingerprint in hyperdiploid patients, characterized by the upregulation of lncRNAs/pseudogenes related to ribosomal protein genes, known to be upregulated in this molecular group. Overall, the data provides an important resource for future studies on the functions of lncRNAs in the pathology.

AB - Although many efforts have recently contributed to improve our knowledge of molecular pathogenesis of multiple myeloma (MM), the role and significance of long non-coding RNAs (lncRNAs) in plasma cells (PC) malignancies remains virtually absent. To this aim, we developed a custom annotation pipeline of microarray data investigating lncRNA expression in PCs from 20 monoclonal gammopathies of undetermined significance, 33 smoldering MM, 170 MM, and 36 extra-medullary MMs/plasma cell leukemia patients, and 9 healthy donors. Our study identified 31 lncRNAs deregulated in tumor samples compared to normal controls; among these, the upregulation of MALAT1 appeared associated in MM patients with molecular pathways involving cell cycle regulation, p53-mediated DNA damage response, and mRNA maturation processes. Furthermore, we found 21 lncRNAs whose expression were progressively deregulated trough the more aggressive stages of PC dyscrasia, suggesting a possible role in the progression of the disease. Finally, in the context of molecular heterogeneity of MM, we identified a transcriptional fingerprint in hyperdiploid patients, characterized by the upregulation of lncRNAs/pseudogenes related to ribosomal protein genes, known to be upregulated in this molecular group. Overall, the data provides an important resource for future studies on the functions of lncRNAs in the pathology.

KW - Expression profiling

KW - LncRNA

KW - MALAT1

KW - Multiple myeloma

KW - Plasma cell dyscrasia

UR - http://www.scopus.com/inward/record.url?scp=84962920479&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962920479&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.7442

DO - 10.18632/oncotarget.7442

M3 - Article

VL - 7

SP - 14814

EP - 14830

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 12

ER -