{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:17:21Z","timestamp":1791274641802,"version":"4.1.0"},"reference-count":46,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,7,5]]},"abstract":"<jats:p>Ataxia telangiectasia mutated (ATM) deficiency predisposes humans and mice to T lineage lymphomas with recurrent chromosome 14 translocations involving the T cell receptor \u03b1\/\u03b4 (Tcra\/d) locus. Such translocations have been thought to result from aberrant repair of DNA double-strand breaks (DSBs) during Tcra locus V(D)J recombination, and to require the Tcra enhancer (E\u03b1) for Tcra rearrangement or expression of the translocated oncogene. We now show that, in addition to the known chromosome 14 translocation, ATM-deficient mouse thymic lymphomas routinely contain a centromeric fragment of chromosome 14 that spans up to the 5\u2032 boundary of the Tcra\/d locus, at which position a 500-kb or larger region centromeric to Tcra\/d is routinely amplified. In addition, they routinely contain a large deletion of the telomeric end of one copy of chromosome 12. In contrast to prior expectations, the recurrent translocations and amplifications involve V(D)J recombination\u2013initiated breaks in the Tcrd locus, as opposed to the Tcra locus, and arise independently of the E\u03b1. Overall, our studies reveal previously unexpected mechanisms that contribute to the oncogenic transformation of ATM-deficient T lineage cells.<\/jats:p>","DOI":"10.1084\/jem.20100285","type":"journal-article","created":{"date-parts":[[2010,6,21]],"date-time":"2010-06-21T22:19:35Z","timestamp":1277158775000},"page":"1369-1380","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":79,"title":["ATM-deficient thymic lymphoma is associated with aberrant\n                    <i>tcrd<\/i>\n                    rearrangement and gene amplification"],"prefix":"10.1084","volume":"207","author":[{"given":"Shan","family":"Zha","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, the Children\u2019s Hospital, the Immune Disease Institute, and the Harvard Medical School, Boston, MA 02115 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig H.","family":"Bassing","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, the Children\u2019s Hospital, the Immune Disease Institute, and the Harvard Medical School, Boston, MA 02115 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi","family":"Sanda","sequence":"additional","affiliation":[{"name":"Dana-Faber Cancer Institute, the Harvard Medical School, Boston, MA 02115 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Brush","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, the Children\u2019s Hospital, the Immune Disease Institute, and the Harvard Medical School, Boston, MA 02115 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harin","family":"Patel","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, the Children\u2019s Hospital, the Immune Disease Institute, and the Harvard Medical School, Boston, MA 02115 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Goff","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, the Children\u2019s Hospital, the Immune Disease Institute, and the Harvard Medical School, Boston, MA 02115 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, the Children\u2019s Hospital, the Immune Disease Institute, and the Harvard Medical School, Boston, MA 02115 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suprawee","family":"Tepsuporn","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, the Children\u2019s Hospital, the Immune Disease Institute, and the Harvard Medical School, Boston, MA 02115 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Gatti","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Laboratory Medicine, the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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