{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:00:51Z","timestamp":1791414051315,"version":"4.3.3"},"reference-count":19,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,4,30]]},"abstract":"<jats:p>Acute lymphoblastic leukemia (ALL) is the major pediatric cancer. At diagnosis, the developmental timing of mutations contributing critically to clonal diversification and selection can be buried in the leukemia's covert natural history. Concordance of ALL in monozygotic, monochorionic twins is a consequence of intraplacental spread of an initiated preleukemic clone. Studying monozygotic twins with ALL provides a unique means of uncovering the timeline of mutations contributing to clonal evolution, pre- and postnatally. We sequenced the whole genomes of leukemic cells from two twin pairs with ALL to comprehensively characterize acquired somatic mutations in ALL, elucidating the developmental timing of all genetic lesions. Shared, prenatal, coding-region single-nucleotide variants were limited to the putative initiating lesions. All other nonsynonymous single-nucleotide variants were distinct between tumors and, therefore, secondary and postnatal. These changes occurred in a background of noncoding mutational changes that were almost entirely discordant in twin pairs and likely passenger mutations acquired during leukemic cell proliferation.<\/jats:p>","DOI":"10.1073\/pnas.1221099110","type":"journal-article","created":{"date-parts":[[2013,4,8]],"date-time":"2013-04-08T21:18:31Z","timestamp":1365455911000},"page":"7429-7433","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":49,"title":["Developmental timing of mutations revealed by whole-genome sequencing of twins with acute lymphoblastic leukemia"],"prefix":"10.1073","volume":"110","author":[{"given":"Yussanne","family":"Ma","sequence":"first","affiliation":[{"name":"Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Dobbins","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Sherborne","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Chubb","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Galbiati","sequence":"additional","affiliation":[{"name":"Centro Ricerca Tettamanti, Clinica Pediatrica, Universit\u00e0 di Milano-Bicocca, Ospedale San Gerardo, 20900 Monza (Mi), Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cazzaniga","sequence":"additional","affiliation":[{"name":"Centro Ricerca Tettamanti, Clinica Pediatrica, Universit\u00e0 di Milano-Bicocca, Ospedale San Gerardo, 20900 Monza (Mi), Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Micalizzi","sequence":"additional","affiliation":[{"name":"Experimental Clinical Hematology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) G. Gaslini, 16148 Genova, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick","family":"Tearle","sequence":"additional","affiliation":[{"name":"Complete Genomics, Inc., Mountain View, CA 94043;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Hain","sequence":"additional","affiliation":[{"name":"Paediatric Palliative Medicine, Children's Hospital for Wales, University Hospital of Wales, Cardiff CF14 4XW, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mel","family":"Greaves","sequence":"additional","affiliation":[{"name":"Haemato-Oncology Research Unit, Division of Molecular Pathology, Institute of Cancer Research, Surrey SM2 5NG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Houlston","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,4,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-12-3817"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09650"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-338848"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1150648"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.112218799"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05690"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-251413"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10738"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10725"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05036.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181498"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09744"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11247"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.06.023"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198056"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10733"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10910"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6861907"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.092759.109"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1221099110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T22:34:32Z","timestamp":1649802872000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1221099110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,8]]},"references-count":19,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2013,4,30]]}},"alternative-id":["10.1073\/pnas.1221099110"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1221099110","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717998605.793475805","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,8]]},"assertion":[{"value":"2013-04-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}