{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T15:32:27Z","timestamp":1773761547349,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,11,20]],"date-time":"2003-11-20T00:00:00Z","timestamp":1069286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2004,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A major feature of ataxia\u2010telangiectasia (A\u2010T) is an increased risk of cancer, particularly of lymphoid malignancies. We studied <jats:italic>ATM<\/jats:italic> gene involvement in leukemic cells derived from 39 pediatric T\u2010cell acute lymphoblastic leukemias (ALLs). Two types of sequence changes\u2014truncating and missense\u2014were identified in 8 T\u2010cell ALL samples: 3 truncating changes, all previously identified in A\u2010T (R35X, \u221230del215, 2284delCT), and 3 missense variants (V410A, F582L, F1463C) were found, none associated with loss of heterozygosity (LOH). In all patients studied, the mutation was present in the germ\u2010line. A\u2010T carriers, defined by the finding of truncating mutations, were found to be 12.9 times more frequent than in the normal population (<jats:italic>P<\/jats:italic> = 0.004). A normally ethnically matched population was screened for the 3 missense variants, and their frequency was significantly more prevalent (4.9\u2010fold excess) than in the normal population (<jats:italic>P<\/jats:italic> = 0.03). Our data suggest there is some evidence of an association between missense alterations in the <jats:italic>ATM<\/jats:italic> gene and T\u2010cell ALL. A significant difference in the mean age at diagnosis of T\u2010cell ALL was noted between patients harboring an <jats:italic>ATM<\/jats:italic> sequence change and those with no change, 5.4 years and 9.7 years, respectively (<jats:italic>P<\/jats:italic> = 0.001). No <jats:italic>ATM<\/jats:italic> alterations were identified in relapse samples, indicating that <jats:italic>ATM<\/jats:italic> does not play a role in disease progression. The high prevalence of germ\u2010line truncating and missense <jats:italic>ATM<\/jats:italic> gene alterations among children with sporadic T\u2010cell ALL suggests an association with susceptibility to T\u2010cell acute leukemia and supports the model of predisposition to cancer in A\u2010T heterozygotes. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.10306","type":"journal-article","created":{"date-parts":[[2003,12,23]],"date-time":"2003-12-23T10:01:47Z","timestamp":1072173707000},"page":"161-166","source":"Crossref","is-referenced-by-count":40,"title":["Germ\u2010line <i>ATM<\/i> gene alterations are associated with susceptibility to sporadic T\u2010cell acute lymphoblastic leukemia in children"],"prefix":"10.1002","volume":"39","author":[{"given":"Ella","family":"Liberzon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Smadar","family":"Avigad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Batia","family":"Stark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Zilberstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Freedman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malka","family":"Gorfine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herzel","family":"Gavriel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian 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