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We found a frequent allelic expression imbalance between the missense mutant and wild-type\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    alleles in breast tumors from the METABRIC (70.2%) and the TCGA (60.1%) projects. When considering the mechanisms controlling allelic expression, 27.7% and 11.8% of tumors showed imbalance due to regulatory variants in cis, in the two studies respectively. Furthermore, preferential expression of the mutant allele due to cis-regulatory variation is associated with poor prognosis in the METABRIC tumors (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.031). Interestingly, ER\u2212, PR\u2212, and HER2+ tumors showed significant preferential expression of the mutated allele in both datasets. Our work provides compelling evidence to support the clinical utility of\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    allelic expression in breast cancer in identifying patients of poorer prognosis, and those with low expression of the mutated allele, who will unlikely benefit from PI3K inhibitors. Furthermore, our work proposes a model of differential regulation of a critical cancer-promoting gene in breast cancer.\n                  <\/jats:p>","DOI":"10.1038\/s41523-022-00435-9","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T06:03:24Z","timestamp":1654668204000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2184-9962","authenticated-orcid":false,"given":"Lizelle","family":"Correia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramiro","family":"Magno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana M.","family":"Xavier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardo P.","family":"de Almeida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filipa","family":"Esteves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marinella","family":"Ghezzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5799-8911","authenticated-orcid":false,"given":"Matthew","family":"Eldridge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9008-2158","authenticated-orcid":false,"given":"Chong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Bosma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenza","family":"Mittempergher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-4772","authenticated-orcid":false,"given":"Ana","family":"Marreiros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8677-3423","authenticated-orcid":false,"given":"Rene","family":"Bernards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3547-1489","authenticated-orcid":false,"given":"Carlos","family":"Caldas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5697-1082","authenticated-orcid":false,"given":"Suet-Feung","family":"Chin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0454-9207","authenticated-orcid":false,"given":"Ana-Teresa","family":"Maia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"435_CR1","first-page":"852\u2013862.e4","volume":"3","author":"CM Bielski","year":"2018","unstructured":"Bielski, C. 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