PMID- 17229636
OWN - NLM
STAT- MEDLINE
DCOM- 20070321
LR  - 20190608
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Linking)
VI  - 92
IP  - 1
DP  - 2007 Jan
TI  - Integrative genomic analysis reveals distinct transcriptional and genetic 
      features associated with chromosome 13 deletion in multiple myeloma.
PG  - 56-65
AB  - BACKGROUND AND OBJECTIVES: The chromosome 13 deletion (Delta13) is one of the 
      most frequent chromosomal alterations in multiple myeloma (MM). Delta13 is 
      associated with an unfavorable prognosis, although there is increasing agreement 
      that its prognostic relevance must be related to the ploidy status and the 
      presence of different chromosomal translocations. The aim of this study was to 
      provide a comprehensive analysis of the transcriptional features of Delta13 in 
      MM. DESIGN AND METHODS: Highly purified plasma cells from 80 newly diagnosed MM 
      patients were characterized by means of fluorescence in situ hybridization (FISH) 
      and high-density oligonucleotide microarray for gene expression profiling and 
      chromosomal alterations. RESULTS: We identified 67 differentially expressed genes 
      in the patients with and without the chromosome 13 deletion, all of which were 
      downregulated in the cases with Delta13: 44 mapped along the whole chromosome 13, 
      seven on chromosome 11 and three on chromosome 19. Functional analyses of the 
      selected genes indicated their involvement in protein biosynthesis, 
      ubiquitination and transcriptional regulation. An integrative genomic approach 
      based on regional analyses of the gene expression data identified distinct 
      chromosomal regions whose global expression modulation could differentiate 
      Delta13-positive cases, in particular the upregulation of 1q21-1q42 and the 
      downregulation of 19p and almost the entire chromosome 11. FISH analyses 
      confirmed the close relationship between Delta13-positivity and the presence of 
      extra copies of 1q21-1q42 (p=6 x 10(-4)) or the absence of chromosome 11 and 19 
      trisomy (p=5 x 10(-4)). INTERPRETATION AND CONCLUSIONS: Our results indicate that 
      distinct types of chromosomal aberrations are closely related to the 
      transcriptional profiles of Delta13-positive cases, suggesting that the 
      contribution of Delta13 to the malignancy should be considered together with 
      associated abnormalities.
FAU - Agnelli, Luca
AU  - Agnelli L
AD  - Centro di Genetica Molecolare ed Espressione Genica, Padiglione G. Marcora, 
      Fondazione IRCCS Ospedale Policlinico, via Francesco Sforza 35, 20122 Milan, 
      Italy.
FAU - Bicciato, Silvio
AU  - Bicciato S
FAU - Fabris, Sonia
AU  - Fabris S
FAU - Baldini, Luca
AU  - Baldini L
FAU - Morabito, Fortunato
AU  - Morabito F
FAU - Intini, Daniela
AU  - Intini D
FAU - Verdelli, Donata
AU  - Verdelli D
FAU - Callegaro, Andrea
AU  - Callegaro A
FAU - Bertoni, Francesco
AU  - Bertoni F
FAU - Lambertenghi-Deliliers, Giorgio
AU  - Lambertenghi-Deliliers G
FAU - Lombardi, Luigia
AU  - Lombardi L
FAU - Neri, Antonino
AU  - Neri A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Chromosome Deletion
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 13/*genetics
MH  - Female
MH  - Gene Expression Profiling
MH  - *Genome, Human
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*genetics
MH  - Oligonucleotide Array Sequence Analysis
MH  - *Transcription, Genetic
MH  - Up-Regulation
EDAT- 2007/01/19 09:00
MHDA- 2007/03/22 09:00
CRDT- 2007/01/19 09:00
PHST- 2007/01/19 09:00 [pubmed]
PHST- 2007/03/22 09:00 [medline]
PHST- 2007/01/19 09:00 [entrez]
AID - 10.3324/haematol.10414 [doi]
PST - ppublish
SO  - Haematologica. 2007 Jan;92(1):56-65. doi: 10.3324/haematol.10414.