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We report the identification of both structural drivers, as well as recurrent non-coding variation in promoters. Additionally we found the transcriptional profile of histone gene cluster 1 and <jats:italic>CTCF<\/jats:italic> altered tumours shared hallmarks of hyperdiploid ALL suggesting a \u2018hyperdiploid like\u2019 subtype. ALL subtypes are driven by distinct mutational processes with AID mutagenesis being confined to <jats:italic>ETV6-RUNX1<\/jats:italic> tumours. Subclonality is a ubiquitous feature of ALL, consistent with Darwinian evolution driving selection and expansion of tumours. Driver mutations in B-cell developmental genes (<jats:italic>IKZF1, PAX5, ZEB2<\/jats:italic>) tend to be clonal and RAS\/RTK mutations subclonal. In addition to identifying new avenues for therapeutic exploitation, this analysis highlights that targeted therapies should take into account composite mutational profile and clonality.<\/jats:p>","DOI":"10.1038\/s41408-021-00570-9","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T13:03:39Z","timestamp":1636463019000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Cancer drivers and clonal dynamics in acute lymphoblastic leukaemia subtypes"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7157-754X","authenticated-orcid":false,"given":"James B.","family":"Studd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3966-3501","authenticated-orcid":false,"given":"Alex J.","family":"Cornish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-8525","authenticated-orcid":false,"given":"Phuc H.","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9663-4611","authenticated-orcid":false,"given":"Philip","family":"Law","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1783-6296","authenticated-orcid":false,"given":"Ben","family":"Kinnersley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5268-0242","authenticated-orcid":false,"given":"Richard","family":"Houlston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"key":"570_CR1","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1016\/S0140-6736(12)62187-4","volume":"381","author":"H Inaba","year":"2013","unstructured":"Inaba H, Greaves M, Mullighan CG. 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