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We report on incidence, distribution, and features of chromothriptic events in T-cell acute lymphoblastic leukemias (T-ALL). SNP array was performed in 103 T-ALL (39 ETP\/near ETP, 59 non-ETP, and 5 with unknown stage of differentiation), including 38 children and 65 adults. Chromothripsis was detected in 11.6% of all T-ALL and occurred only in adult cases with an immature phenotype (12\/39 cases; 30%). It affected 1 to 4 chromosomes, and recurrently involved chromosomes 1, 6, 7, and 17. Abnormalities of genes typically associated with T-ALL were found at breakpoints of chromothripsis. In addition, it gave rise to new\/rare alterations, such as, the <jats:italic>SFPQ::ZFP36L2<\/jats:italic> fusion, reported in pediatric T-ALL, deletions of putative suppressors, such as <jats:italic>IKZF2<\/jats:italic> and <jats:italic>CSMD1<\/jats:italic>, and amplification of the <jats:italic>B<\/jats:italic>C<jats:italic>L2<\/jats:italic> gene. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of <jats:italic>MYCN<\/jats:italic> expression, and a significant downregulation of <jats:italic>RGCC<\/jats:italic>, which is typically induced by <jats:italic>TP53<\/jats:italic> in response to DNA damage. Furthermore we identified mutations and\/or deletions of DNA repair\/genome stability genes in all cases, and an association with <jats:italic>NUP214<\/jats:italic> rearrangements in 33% of cases.<\/jats:p>","DOI":"10.1038\/s41375-022-01671-5","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T19:02:23Z","timestamp":1660676543000},"page":"2577-2585","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults"],"prefix":"10.1038","volume":"36","author":[{"given":"Silvia","family":"Arniani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Pierini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Pellanera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Matteucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danika","family":"Di Giacomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Bardelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Quintini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Mavridou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5653-8307","authenticated-orcid":false,"given":"Anair Graciela","family":"Lema Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Nardelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Moretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gorello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Crescenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Romoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Beacci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-3100","authenticated-orcid":false,"given":"Marco","family":"Cerrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Fracchiolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Sica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Forghieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4755-9533","authenticated-orcid":false,"given":"Fabio","family":"Giglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Dargenio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredana","family":"Elia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-9846","authenticated-orcid":false,"given":"Roberta","family":"La Starza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-0148","authenticated-orcid":false,"given":"Cristina","family":"Mecucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"1671_CR1","doi-asserted-by":"publisher","unstructured":"Bardelli V, Arniani S, Pierini V, Di Giacomo D, Pierini T, Gorello P, et al. 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