PMID- 21078186
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 1755-8166 (Electronic)
IS  - 1755-8166 (Linking)
VI  - 3
DP  - 2010 Nov 15
TI  - Assessing karyotype precision by microarray-based comparative genomic 
      hybridization in the myelodysplastic/myeloproliferative syndromes.
PG  - 23
LID - 10.1186/1755-8166-3-23 [doi]
AB  - BACKGROUND: Recent genome-wide microarray-based research investigations have 
      revealed a high frequency of submicroscopic copy number alterations (CNAs) in the 
      myelodysplastic syndromes (MDS), suggesting microarray-based comparative genomic 
      hybridization (aCGH) has the potential to detect new clinically relevant genomic 
      markers in a diagnostic laboratory. RESULTS: We performed an exploratory study on 
      30 cases of MDS, myeloproliferative neoplasia (MPN) or evolving acute myeloid 
      leukemia (AML) (% bone marrow blasts </= 30%, range 0-30%, median, 8%) by aCGH, 
      using a genome-wide bacterial artificial chromosome (BAC) microarray. The sample 
      data were compared to corresponding cytogenetics, fluorescence in situ 
      hybridization (FISH), and clinical-pathological findings. Previously unidentified 
      imbalances, in particular those considered submicroscopic aberrations (< 10 Mb), 
      were confirmed by FISH analysis. CNAs identified by aCGH were concordant with the 
      cytogenetic/FISH results in 25/30 (83%) of the samples tested. aCGH revealed new 
      CNAs in 14/30 (47%) patients, including 28 submicroscopic or hidden aberrations 
      verified by FISH studies. Cryptic 344-kb RUNX1 deletions were found in three 
      patients at time of AML transformation. Other hidden CNAs involved 3q26.2/EVI1, 
      5q22/APC, 5q32/TCERG1,12p13.1/EMP1, 12q21.3/KITLG, and 17q11.2/NF1. Gains of 
      CCND2/12p13.32 were detected in two patients. aCGH failed to detect a balanced 
      translocation (n = 1) and low-level clonality (n = 4) in five karyotypically 
      aberrant samples, revealing clinically important assay limitations. CONCLUSIONS: 
      The detection of previously known and unknown genomic alterations suggests that 
      aCGH has considerable promise for identification of both recurring microscopic 
      and submicroscopic genomic imbalances that contribute to myeloid disease 
      pathogenesis and progression. These findings suggest that development of 
      higher-resolution microarray platforms could improve karyotyping in clinical 
      practice.
FAU - Slovak, Marilyn L
AU  - Slovak ML
AD  - Signature Genomics, Spokane, WA, USA. shaffer@signaturegenomics.com.
FAU - Smith, David D
AU  - Smith DD
FAU - Bedell, Victoria
AU  - Bedell V
FAU - Hsu, Ya-Hsuan
AU  - Hsu YH
FAU - O'Donnell, Margaret
AU  - O'Donnell M
FAU - Forman, Stephen J
AU  - Forman SJ
FAU - Gaal, Karl
AU  - Gaal K
FAU - McDaniel, Lisa
AU  - McDaniel L
FAU - Schultz, Roger
AU  - Schultz R
FAU - Ballif, Blake C
AU  - Ballif BC
FAU - Shaffer, Lisa G
AU  - Shaffer LG
LA  - eng
PT  - Journal Article
DEP - 20101115
PL  - England
TA  - Mol Cytogenet
JT  - Molecular cytogenetics
JID - 101317942
PMC - PMC3000833
EDAT- 2010/11/17 06:00
MHDA- 2010/11/17 06:01
PMCR- 2010/11/15
CRDT- 2010/11/17 06:00
PHST- 2010/10/07 00:00 [received]
PHST- 2010/11/15 00:00 [accepted]
PHST- 2010/11/17 06:00 [entrez]
PHST- 2010/11/17 06:00 [pubmed]
PHST- 2010/11/17 06:01 [medline]
PHST- 2010/11/15 00:00 [pmc-release]
AID - 1755-8166-3-23 [pii]
AID - 10.1186/1755-8166-3-23 [doi]
PST - epublish
SO  - Mol Cytogenet. 2010 Nov 15;3:23. doi: 10.1186/1755-8166-3-23.