{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:43:06Z","timestamp":1773153786194,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,3,17]],"date-time":"2003-03-17T00:00:00Z","timestamp":1047859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"L'Association pour la Recherche contre le Cancer (ARC)"},{"name":"Le Comit\u00e9 de Paris de la Ligue contre le Cancer"},{"DOI":"10.13039\/501100004431","name":"La Fondation de France","doi-asserted-by":"crossref","award":["2000002992"],"award-info":[{"award-number":["2000002992"]}],"id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2003,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deletion of the 9p21 chromosomal region is frequently found in childhood acute lymphoblastic leukemia (ALL). The target of these deletions is <jats:italic>CDKN2A<\/jats:italic>, a gene encoding both p16<jats:sup>INK4a<\/jats:sup> and p14<jats:sup>ARF<\/jats:sup>. However, contiguous genes such as <jats:italic>CDKN2B<\/jats:italic>, encoding p15<jats:sup>INK4b<\/jats:sup>, or <jats:italic>MTAP<\/jats:italic>, encoding methylthioadenosine phosphorylase, can be included in the deletions. Gene dosage by use of real\u2010time PCR has recently been proposed as a promising technical option for the diagnosis of deletions. However, its reliability and its capacity to detect mono\u2010allelic deletions in tumor samples are controversial. To evaluate the frequency and extent of deletions in 284 children with ALL, we devised a real\u2010time PCR assay for <jats:italic>CDKN2A<\/jats:italic>, <jats:italic>CDKN2B<\/jats:italic> exons 1\u03b2 and 3, and <jats:italic>MTAP<\/jats:italic> gene dosage and validated it by comparison with loss\u2010of\u2010heterozygosity analysis. We show that, if several controls and adjustments are performed, real\u2010time PCR can provide a reliable test for mono\u2010 and bi\u2010allelic deletions in ALL. We propose a strategy that overcomes the major caveats of such a dosage in tumor samples: aneuploidy and contamination by normal cells. By use of this assay, we found bi\u2010allelic deletions in 58 and 17% of T\u2010 and B\u2010lineage ALL, respectively. Mono\u2010allelic deletion was observed in about 15% of cases, stressing the importance of their detection in ALL. <jats:italic>CDKN2B<\/jats:italic> and\/or <jats:italic>MTAP<\/jats:italic> co\u2010deletions were highly variable in both T\u2010 and B\u2010lineage ALL, making ALL with 9p21 a rather heterogeneous group. Because proteins encoded by these genes might influence the response to treatment, the prognosis of 9p21\u2010deleted ALL could vary according to the extent of the deletion. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.10188","type":"journal-article","created":{"date-parts":[[2003,3,24]],"date-time":"2003-03-24T11:59:12Z","timestamp":1048507152000},"page":"44-57","source":"Crossref","is-referenced-by-count":69,"title":["<i>CDKN2A<\/i>, <i>CDKN2B<\/i>, and <i>MTAP<\/i> gene dosage permits precise characterization of mono\u2010 and bi\u2010allelic 9p21 deletions in childhood acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"37","author":[{"given":"Rapha\u00eblle","family":"Bertin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Acquaviva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delphine","family":"Mirebeau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Guidal\u2010Giroux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etienne","family":"Vilmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Cav\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,3,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10014"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.8.3083.bloodjournal8883083"},{"key":"e_1_2_6_4_1","first-page":"1492","article-title":"Use 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