Journal article
Neurobeachin ( NBEA) is a target of recurrent interstitial deletions at 13q13 in patients with MGUS and multiple myeloma
Experimental hematology, Vol.37(2), pp.234-244
2009
DOI: 10.1016/j.exphem.2008.10.014
PMCID: PMC2868587
PMID: 19135901
Abstract
Chromosome 13 deletions (del[13]), detected by metaphase cytogenetics, predict poor outcomes in multiple myeloma (MM), but the gene(s) responsible have not been conclusively identified. We sought to identify tumor-suppressor genes on chromosome 13 using a novel array comparative genomic hybridization (aCGH) strategy.
We identified DNA copy number losses on chromosome 13 using genomic DNA isolated from CD138-enriched bone marrow cells (tumor) from 20 patients with MM, monoclonal gammopathy of undetermined significance, or amyloidosis. We used matched skin biopsy (germline) genomic DNA to control for copy number polymorphisms and a novel aCGH array dedicated to chromosome 13 to map somatic DNA gains and losses at ultra-high resolution (>385,000 probes; median probe spacing 60 bp). We analyzed microarray expression data from an additional 262 patient samples both with and without del[13].
Two distinct minimally deleted regions at 13q14 and 13q13 were defined that affected the
RB1 and
NBEA genes, respectively.
RB1 is a canonical tumor suppressor previously implicated in MM.
NBEA is implicated in membrane trafficking in neurons, protein kinase A binding, and has no known role in cancer. Noncoding RNAs on chromosome 13 were not affected by interstitial deletions. Both the
RB1 and
NBEA genes were deleted in 40% of cases (8 of 20; 5 patients with del[13] detected by traditional methods and 3 patients with interstitial deletions detected by aCGH). Forty-one additional MM patient samples were used for complete exonic sequencing of
RB1, but no somatic mutations were found. Along with
RB1,
NBEA gene expression was significantly reduced in cases with del[13].
The
NBEA gene at 13q13, and its expression are frequently disrupted in MM. Additional studies are warranted to evaluate the role of
NBEA as a novel candidate tumor-suppressor gene.
Details
- Title: Subtitle
- Neurobeachin ( NBEA) is a target of recurrent interstitial deletions at 13q13 in patients with MGUS and multiple myeloma
- Creators
- Julie O'Neal - Department of Internal Medicine, Division of Oncology, Washington University, Siteman Cancer Center, St Louis, MO, USAFeng Gao - Department of Biostatistics, Washington University, St Louis, MO, USAAnjum Hassan - Department of Pathology and Immunology, Washington University, St Louis, MO, USARyan Monahan - Department of Internal Medicine, Division of Oncology, Washington University, Siteman Cancer Center, St Louis, MO, USASamantha Barrios - Department of Internal Medicine, Division of Oncology, Washington University, Siteman Cancer Center, St Louis, MO, USAIan Lee - Department of Hematology-Oncology, National University Hospital, SingaporeWee J Chng - Department of Hematology-Oncology, National University Hospital, SingaporeRavi Vij - Department of Internal Medicine, Division of Oncology, Washington University, Siteman Cancer Center, St Louis, MO, USAMichael H Tomasson - Department of Internal Medicine, Division of Oncology, Washington University, Siteman Cancer Center, St Louis, MO, USA
- Resource Type
- Journal article
- Publication Details
- Experimental hematology, Vol.37(2), pp.234-244
- DOI
- 10.1016/j.exphem.2008.10.014
- PMID
- 19135901
- PMCID
- PMC2868587
- NLM abbreviation
- Exp Hematol
- ISSN
- 0301-472X
- eISSN
- 1873-2399
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2009
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094382702771
Metrics
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