| Using MS-MLPA as an efficient screening tool for detecting 9p21 abnormalities in pediatric acute lymphoblastic leukemia. | |
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MedLine Citation:
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PMID: 21796768 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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R Brett Gardiner; Barbara A Morash; Christie Riddell; Hao Wang; Conrad V Fernandez; Margaret Yhap; Jason N Berman |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-27 |
Journal Detail:
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Title: Pediatric blood & cancer Volume: - ISSN: 1545-5017 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101186624 Medline TA: Pediatr Blood Cancer Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
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Department of Microbiology and Immunology, IWK Health Centre/Dalhousie University, Halifax, NS, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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