{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:49:53Z","timestamp":1777520993198,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,7,27]],"date-time":"2011-07-27T00:00:00Z","timestamp":1311724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Beatrice Hunter Cancer Institute\/Cancer Care Nova Scotia Norah Stephen Oncology Scholar Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Characterization of recurrent genetic lesions in childhood acute lymphoblastic leukemia (ALL) has enabled therapeutic stratification with improved outcomes. The tumor suppressor genes, <jats:italic>CDKN2A<\/jats:italic> and <jats:italic>CDKN2B<\/jats:italic>, encoding p16<jats:sup>INK4a<\/jats:sup>, p14<jats:sup>ARF<\/jats:sup>, and p15<jats:sup>INK4b<\/jats:sup> have been localized to 9p21. Abnormalities of 9p21 have been reported in 10\u201330% 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\u2010dependent probe amplification (MS\u2010MLPA), remains uncertain, and thus also the prognostic significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>We investigated the incidence and prognostic importance of 9p21 abnormalities in pediatric ALL patients using MS\u2010MLPA and compared these results to FISH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, MS\u2010MLPA 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\u2010MLPA identified five deletions not found by FISH. Aberrant methylation at <jats:italic>CDKN2B<\/jats:italic> was found in 19 (46%) patients. 9p21 abnormalities were associated with National Cancer Institute (NCI) high\u2010risk criteria (<jats:italic>P<\/jats:italic>\u2009=\u20090.04) and were present in all five patients with T\u2010cell disease. Four pre\u2010B\u2010cell ALL patients relapsed, three of whom had prior 9p21 abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MS\u2010MLPA 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\u2010MLPA, 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 2012; 58: 852\u2013859. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.23285","type":"journal-article","created":{"date-parts":[[2011,7,27]],"date-time":"2011-07-27T22:48:47Z","timestamp":1311806927000},"page":"852-859","source":"Crossref","is-referenced-by-count":11,"title":["Using MS\u2010MLPA as an efficient screening tool for detecting 9p21 abnormalities in pediatric acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"58","author":[{"given":"R. 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