PMID- 19357701 OWN - NLM STAT- MEDLINE DCOM- 20090921 LR - 20220318 IS - 1476-5551 (Electronic) IS - 0887-6924 (Linking) VI - 23 IP - 8 DP - 2009 Aug TI - Mesenchymal stem cells from multiple myeloma patients display distinct genomic profile as compared with those from normal donors. PG - 1515-27 LID - 10.1038/leu.2009.65 [doi] AB - It is an open question whether in multiple myeloma (MM) bone marrow stromal cells contain genomic alterations, which may contribute to the pathogenesis of the disease. We conducted an array-based comparative genomic hybridization (array-CGH) analysis to compare the extent of unbalanced genomic alterations in mesenchymal stem cells from 21 myeloma patients (MM-MSCs) and 12 normal donors (ND-MSCs) after in vitro culture expansion. Whereas ND-MSCs were devoid of genomic imbalances, several non-recurrent chromosomal gains and losses (>1 Mb size) were detected in MM-MSCs. Using real-time reverse transcription PCR, we found correlative deregulated expression for five genes encoded in regions for which genomic imbalances were detected using array-CGH. In addition, only MM-MSCs showed a specific pattern of 'hot-spot' regions with discrete (<1 Mb) genomic alterations, some of which were confirmed using fluorescence in situ hybridization (FISH). Within MM-MSC samples, unsupervised cluster analysis did not correlate with particular clinicobiological features of MM patients. We also explored whether cytogenetic abnormalities present in myelomatous plasma cells (PCs) were shared by matching MSCs from the same patients using FISH. All MM-MSCs were cytogenetically normal for the tested genomic alterations. Therefore we cannot support a common progenitor for myeloma PCs and MSCs. FAU - Garayoa, M AU - Garayoa M AD - Centro de Investigacion del Cancer, Instituto de Biologia Molecular y Celular del Cancer, Universidad de Salamanca-CSIC, Salamanca, Spain. mgarayoa@usal.es FAU - Garcia, J L AU - Garcia JL FAU - Santamaria, C AU - Santamaria C FAU - Garcia-Gomez, A AU - Garcia-Gomez A FAU - Blanco, J F AU - Blanco JF FAU - Pandiella, A AU - Pandiella A FAU - Hernandez, J M AU - Hernandez JM FAU - Sanchez-Guijo, F M AU - Sanchez-Guijo FM FAU - del Canizo, M-C AU - del Canizo MC FAU - Gutierrez, N C AU - Gutierrez NC FAU - San Miguel, J F AU - San Miguel JF LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090409 PL - England TA - Leukemia JT - Leukemia JID - 8704895 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Bone Marrow/pathology MH - Bone Marrow Cells/chemistry MH - Cell Lineage MH - Cells, Cultured/chemistry MH - Cluster Analysis MH - *Comparative Genomic Hybridization MH - Female MH - Gene Dosage MH - Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Mesenchymal Stem Cells/*chemistry MH - Middle Aged MH - Multiple Myeloma/*genetics/pathology MH - Neoplastic Stem Cells/chemistry MH - Oligonucleotide Array Sequence Analysis MH - Plasma Cells/chemistry MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Cells, Cultured/chemistry EDAT- 2009/04/10 09:00 MHDA- 2009/09/22 06:00 CRDT- 2009/04/10 09:00 PHST- 2009/04/10 09:00 [entrez] PHST- 2009/04/10 09:00 [pubmed] PHST- 2009/09/22 06:00 [medline] AID - leu200965 [pii] AID - 10.1038/leu.2009.65 [doi] PST - ppublish SO - Leukemia. 2009 Aug;23(8):1515-27. doi: 10.1038/leu.2009.65. Epub 2009 Apr 9.