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Using MS-MLPA as an efficient screening tool for detecting 9p21 abnormalities in pediatric acute lymphoblastic leukemia.
MedLine Citation:
PMID:  21796768     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Characterization of recurrent genetic lesions in childhood acute lymphoblastic leukemia (ALL) has enabled therapeutic stratification with improved outcomes. The tumor suppressor genes, CDKN2A and CDKN2B, encoding p16(INK4a) , p14(ARF) , and p15(INK4b) have been localized to 9p21. Abnormalities of 9p21 have been reported in 10-30% of childhood ALL using conventional cytogenetics and fluorescence in situ hybridization (FISH). The incidence of 9p21 using more sensitive techniques, such as methylation specific multiplex ligation-dependent probe amplification (MS-MLPA), remains uncertain, and thus also the prognostic significance. PROCEDURE: We investigated the incidence and prognostic importance of 9p21 abnormalities in pediatric ALL patients using MS-MLPA and compared these results to FISH. RESULTS: In total, MS-MLPA or FISH detected aberrations (both dosage and methylation abnormalities) at 9p21 in a remarkable 32/48 (67%) patients in contrast to a much lower rate of only 8% of patients identified to have deletions by standard G banding cytogenetics. MS-MLPA identified five deletions not found by FISH. Aberrant methylation at CDKN2B was found in 19 (46%) patients. 9p21 abnormalities were associated with National Cancer Institute (NCI) high-risk criteria (P = 0.04) and were present in all five patients with T-cell disease. Four pre-B-cell ALL patients relapsed, three of whom had prior 9p21 abnormalities. CONCLUSIONS: MS-MLPA had a higher detection rate for 9p21 abnormalities than previously reported for other techniques. Given the ease of processing, minimal equipment and low cost of MS-MLPA, our results suggest that previous reports may have underestimated the true frequency of 9p21 abnormalities and their potential impact upon ALL outcome. Pediatr Blood Cancer © 2011 Wiley-Liss, Inc.
Authors:
R Brett Gardiner; Barbara A Morash; Christie Riddell; Hao Wang; Conrad V Fernandez; Margaret Yhap; Jason N Berman
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-27
Journal Detail:
Title:  Pediatric blood & cancer     Volume:  -     ISSN:  1545-5017     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101186624     Medline TA:  Pediatr Blood Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Affiliation:
Department of Microbiology and Immunology, IWK Health Centre/Dalhousie University, Halifax, NS, Canada.
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