title: Genomic studies of multiple myeloma reveal an association between X chromosome alterations and genomic profile complexity.
abstract: The genomic profile of multiple myeloma (MM) has prognostic value by dividing patients into a good prognosis hyperdiploid group and a bad prognosis nonhyperdiploid group with a higher incidence of IGH translocations. This classification, however, is inadequate and many other parameters like mutations, epigenetic modifications, and genomic heterogeneity may influence the prognosis. We performed a genomic study by array-based comparative genomic hybridization on a cohort of 162 patients to evaluate the frequency of genomic gains and losses. We identified a high frequency of X chromosome alterations leading to partial Xq duplication, often associated with inactive X (Xi) deletion in female patients. This partial X duplication could be a cytogenetic marker of aneuploidy as it is correlated with a high number of chromosomal breakages. Patient with high level of chromosomal breakage had reduced survival regardless the region implicated. A higher transcriptional level was shown for genes with potential implication in cancer and located in this altered region. Among these genes, IKBKG and IRAK1 are members of the NFKB pathway which plays an important role in MM and is a target for specific treatments. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratory of Human Genetics, University of Liège, GIGA-Research, Liège, Belgium.
authors.forename: Tiberio
authors.initials: T
authors.lastname: Sticca
authors.affiliation: Department of Human Genetics, University Hospital (CHU), Liège, Belgium.
authors.forename: Jean-Hubert
authors.initials: JH
authors.lastname: Caberg
authors.affiliation: Laboratory of Human Genetics, University of Liège, GIGA-Research, Liège, Belgium.
authors.forename: Stephane
authors.initials: S
authors.lastname: Wenric
authors.affiliation: Laboratory of Human Genetics, University of Liège, GIGA-Research, Liège, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Poulet
authors.affiliation: Department of Human Genetics, University Hospital (CHU), Liège, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Herens
authors.affiliation: Department of Human Genetics, University Hospital (CHU), Liège, Belgium.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Jamar
authors.affiliation: Laboratory of Human Genetics, University of Liège, GIGA-Research, Liège, Belgium.
authors.forename: Claire
authors.initials: C
authors.lastname: Josse
authors.affiliation: Laboratory of Human Genetics, University of Liège, GIGA-Research, Liège, Belgium.
authors.forename: Sonia
authors.initials: S
authors.lastname: El Guendi
authors.affiliation: Department of Hematology and Immuno-Hematology, University Hospital (CHU), Liège, Belgium.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Max
authors.affiliation: Laboratory of Hematology, University of Liège, GIGA-Research, Liège, Belgium.|Department of Clinical Hematology, University Hospital (CHU), Liège, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Beguin
authors.affiliation: Department of Hematology and Immuno-Hematology, University Hospital (CHU), Liège, Belgium.
authors.forename: André
authors.initials: A
authors.lastname: Gothot
authors.affiliation: Laboratory of Hematology, University of Liège, GIGA-Research, Liège, Belgium.|Department of Clinical Hematology, University Hospital (CHU), Liège, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Caers
authors.affiliation: Laboratory of Human Genetics, University of Liège, GIGA-Research, Liège, Belgium.|Department of Human Genetics, University Hospital (CHU), Liège, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bours
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D005500:Follow-Up Studies; D023281:Genomics / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor