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Among the others, a fraction may carry mutations in rarer BC genes, such as <jats:italic>TP53<\/jats:italic>, <jats:italic>STK11<\/jats:italic>, <jats:italic>CDH1<\/jats:italic> and <jats:italic>PTEN.<\/jats:italic> As the identification of women harboring such mutations allows for targeted risk-management, the knowledge of associated manifestations and an accurate clinical and family history evaluation are warranted.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentation<\/jats:title>\n            <jats:p>We describe the case of a woman who developed an infiltrating ductal carcinoma of the right breast at the age of 32, a contralateral BC at age 36 and another BC of the right breast at 40. When she was 39\u00a0years-old, during a dermatological examination, mucocutaneous features suggestive of Cowden Syndrome, a disorder associated to germ-line <jats:italic>PTEN<\/jats:italic> mutations, were noticed. <jats:italic>PTEN<\/jats:italic> genetic testing revealed the novel c.71A &gt; T (p.Asp24Val) mutation, whose deleterious effect, suggested by conservation data and <jats:italic>in silico<\/jats:italic> tools, was definitely demonstrated by the incapacity of mutant PTEN to inhibit Akt phosphorylation when used to complement PTEN-null cells. In BC tissue, despite the absence of LOH or somatic mutations of <jats:italic>PTEN<\/jats:italic>, Akt phosphorylation was markedly increased in comparison to normal tissue, thus implying additional somatic events into the deregulation of the PI3K\/Akt\/mTOR pathway and, presumably, into carcinogenesis. Hence, known oncogenic mutations in <jats:italic>PIK3CA<\/jats:italic> (exons 10 and 21) and <jats:italic>AKT1<\/jats:italic> (exon 2) were screened in tumor DNA with negative results, which suggests that the responsible somatic event(s) is a different, uncommon one.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This case stresses the importance of clinical\/genetic assessment of early-onset BC patients in order to identify mutation carriers, who are at high risk of new events, so requiring tailored management. Moreover, it revealed a novel <jats:italic>PTEN<\/jats:italic> mutation with pathogenic effect, pointing out, however, the need for further efforts to elucidate the molecular steps of <jats:italic>PTEN-<\/jats:italic>associated carcinogenesis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-14-70","type":"journal-article","created":{"date-parts":[[2014,2,6]],"date-time":"2014-02-06T06:02:37Z","timestamp":1391666557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A novel deleterious PTEN mutation in a patient with early-onset bilateral breast cancer"],"prefix":"10.1186","volume":"14","author":[{"given":"Laura Maria","family":"Pradella","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Evangelisti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Ligorio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Ceccarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iria","family":"Neri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Zuntini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura Benedetta","family":"Amato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto Maria","family":"Martelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Gasparre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Turchetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,2,6]]},"reference":[{"issue":"16","key":"4291_CR1","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1016\/S0959-8049(00)00287-2","volume":"36","author":"D Turchetti","year":"2000","unstructured":"Turchetti D, Cortesi L, Federico M, Bertoni C, Mangone L, Ferrari S, Silingardi V: BRCA1 mutations and clinicopathological features in a sample of Italian women with early-onset breast cancer. 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