title: The translocation t(4;14) can be present only in minor subclones in multiple myeloma.
abstract: OBJECTIVE
  Although the translocation t(4;14) is supposed to be a primary event in multiple myeloma, we have been surprised to observe that in large relapse series of patients, the t(4;14) can be observed only in subpopulations of plasma cells, in contrast to what is seen at diagnosis. This observation raised the question of possible subclones harboring the translocation that would be observable only at the time of relapse.
  
  
  METHODS
  To address this issue, we analyzed by FISH a cohort of 306 patients for whom we had at least two samples obtained at different disease phases.
  
  
  RESULTS
  We observed a "gain" of the t(4;14) in 14 patients, and conversely, a "loss" of the translocation in 11 patients. Two hypotheses were raised: either an acquisition of the translocation during evolution or the existence of small t(4;14)-positive subclones at the time of diagnosis. To address this question, we had the opportunity to analyze two patients at the time of diagnosis by RT-PCR (reverse transcription-polymerase chain reaction) to look for the chimeric Eμ-MMSET transcript, and one patient positive at diagnosis, but negative at relapse. The samples were positive, supporting the second hypothesis. Furthermore, the IGH sequences of two patients who "lose" the t(4;14) were identical at diagnosis and relapse, confirming the existence of a common ancestral clone.
  
  
  CONCLUSIONS
  Thus, the conclusion of this study is that the t(4;14) is not a primary event in multiple myeloma and that it can be present in silent subclones at diagnosis, but also at relapse.
authors.affiliation: Unité de Génomique du Myélome, CHU, Dijon, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hébraud
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.forename: Jill
authors.initials: J
authors.lastname: Corre
authors.forename: Gérald
authors.initials: G
authors.lastname: Marit
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Laurence
authors.initials: L
authors.lastname: Lodé
authors.forename: Marc
authors.initials: M
authors.lastname: Wetterwald
authors.forename: Mamoun
authors.initials: M
authors.lastname: Dib
authors.forename: Philippe
authors.initials: P
authors.lastname: Rodon
authors.forename: Laurent
authors.initials: L
authors.lastname: Voillat
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.forename: Eric
authors.initials: E
authors.lastname: Voog
authors.forename: Olivier
authors.initials: O
authors.lastname: Fitoussi
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Stoppa
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kolb
authors.forename: Michel
authors.initials: M
authors.lastname: Maigre
authors.forename: Nadine
authors.initials: N
authors.lastname: Boullanger
authors.forename: Olivier
authors.initials: O
authors.lastname: Allangba
authors.forename: Lionel
authors.initials: L
authors.lastname: Karlin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Daguindau
authors.forename: Laurence
authors.initials: L
authors.lastname: Legros
authors.forename: Claudine
authors.initials: C
authors.lastname: Sohn
authors.forename: Marie-Véronique
authors.initials: MV
authors.lastname: Joubert
authors.forename: Pascal
authors.initials: P
authors.lastname: Lenain
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
mesh_terms: D000368:Aged; D001483:Base Sequence; D019070:Cell Lineage; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000302:isolation & purification; D014178:Translocation, Genetic
chemical_list: C115494:IgH-MMSET fusion protein, human; D015514:Oncogene Proteins, Fusion