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Each deaminase is identified by the <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> nucleotide sequence (\u201cmotif\u201d) surrounding the nucleotide targeted for deamination. The primary objective of this study is to develop an <jats:italic>in silico<\/jats:italic> approach to identify nucleotide sequence changes of the target motifs of key deaminases during oncogenesis. If successful, a secondary objective is to investigate if such changes are associated with disease progression indicators that include disease stage and progression\u2010free survival time. Using a discovery cohort of 194 high\u2010grade serous ovarian adenocarcinoma (<jats:styled-content style=\"fixed-case\">HGS<\/jats:styled-content>\u2010OvCa) exomes, the results confirm the ability of the novel <jats:italic>in silico<\/jats:italic> approach used to identify changes in the preferred target motifs for <jats:styled-content style=\"fixed-case\">AID<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> APOBEC<\/jats:styled-content>3G, <jats:styled-content style=\"fixed-case\">APOBEC<\/jats:styled-content>3B, and <jats:styled-content style=\"fixed-case\">ADAR<\/jats:styled-content>1 during oncogenesis. Using this approach, a set of new cancer\u2010progression associated signatures (C\u2010<jats:styled-content style=\"fixed-case\">PAS<\/jats:styled-content>s) were identified. Furthermore, it was found that the C\u2010<jats:styled-content style=\"fixed-case\">PAS<\/jats:styled-content> identified can be used to differentiate between the cohort of patients that remained progression\u2010free for longer than 60\u00a0months, from those in which disease progressed within 60\u00a0months (sensitivity 95%, specificity 90%). The spectrum of outcomes observed here could provide a foundation for future clinical assessment of susceptibility variants in ovarian, and several other cancers as disease progresses. The ability of the <jats:italic>in silico<\/jats:italic> methodology used to identify changes in deaminase motifs during oncogenesis also suggests new links between immune system function and tumorigenesis.<\/jats:p>","DOI":"10.1002\/cam4.825","type":"journal-article","created":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T11:00:38Z","timestamp":1470222038000},"page":"2629-2640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Association between targeted somatic mutation (TSM) signatures and HGS\u2010OvCa progression"],"prefix":"10.1002","volume":"5","author":[{"given":"Robyn A.","family":"Lindley","sequence":"first","affiliation":[{"name":"Department of Pathology University of Melbourne  Parkville Victoria 3010 Australia"},{"name":"GMDx Pty Ltd  Melbourne Victoria 3000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Humbert","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Melbourne  Parkville Victoria 3010 Australia"},{"name":"Department of Biochemistry and Molecular Biology University of Melbourne  Parkville Victoria 3010 Australia"},{"name":"Cell Cycle and Cancer Genetics Laboratory Peter MacCallum Cancer Centre  East Melbourne Victoria 3002 Australia"},{"name":"Sir Peter MacCallum Department of Oncology University of Melbourne  Parkville Victoria 3010 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cliff","family":"Larner","sequence":"additional","affiliation":[{"name":"Swinburne University of Technology  Hawthorn Victoria 3132 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric H.","family":"Akmeemana","sequence":"additional","affiliation":[{"name":"HealthIQ Pty Ltd  Melbourne Victoria 3000 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5789-4397","authenticated-orcid":false,"given":"Christopher R. 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