{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:14:29Z","timestamp":1790252069917,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Prostatic intraepithelial neoplasia\u2010like (PIN\u2010like) ductal carcinoma is a rare tumour characterised by often cystically dilated glands architecturally resembling high\u2010grade PIN, but lacking basal cells. These tumours are frequently accompanied by grade group 1 acinar cancer and behave relatively indolently. In contrast, conventional ductal adenocarcinoma of the prostate is an aggressive variant comparable to grade group 4 acinar cancer. Here, we used targeted next\u2010generation sequencing to molecularly profile PIN\u2010like ductal carcinoma cases at radical prostatectomy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Five PIN\u2010like ductal carcinoma samples at radical prostatectomy with sufficient tumour tissue available were analysed for genomic alterations by targeted next\u2010generation sequencing using the Johns Hopkins University (JHU) solid tumour panel. DNA was captured using SureSelect for 640 genes and sequenced on the Illumina HiSeq platform. Three of five (60%) of the PIN\u2010like ductal carcinomas showed activating mutations in the RAS\/RAF pathways, which are extraordinarily rare in conventional primary prostate carcinoma (&lt;3% of cases), including an activating hot\u2010spot <jats:italic>BRAF<\/jats:italic> mutation (p.K601E), an activating hot\u2010spot mutation in <jats:italic>HRAS<\/jats:italic> (p.Q61K) and an in\u2010frame activating deletion in <jats:italic>BRAF<\/jats:italic> (p.T488_Q493delinsK). An additional two cases lacked <jats:italic>BRAF<\/jats:italic> or <jats:italic>HRAS<\/jats:italic> mutations, but harboured in\u2010frame insertions of uncertain significance in <jats:italic>MAP2K4<\/jats:italic> and <jats:italic>MAP3K6<\/jats:italic>. One case had sufficient acinar tumour for sequencing, and showed a similar molecular profile as the concurrent PIN\u2010like ductal carcinoma, suggesting a clonal relationship between the two components.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PIN\u2010like ductal carcinoma represents a molecularly unique tumour, enriched for potentially targetable oncogenic driver mutations in the RAS\/RAF\/MAPK pathway. This molecular profile contrasts with that of conventional ductal adenocarcinoma, which is typically enriched for pathogenic mutations in the mismatch repair (MMR) and homologous recombination (HR) DNA repair pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14224","type":"journal-article","created":{"date-parts":[[2020,8,2]],"date-time":"2020-08-02T15:34:08Z","timestamp":1596382448000},"page":"327-333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["PIN\u2010like ductal carcinoma of the prostate has frequent activating RAS\/RAF mutations"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1178-7596","authenticated-orcid":false,"given":"Harsimar B","family":"Kaur","sequence":"first","affiliation":[{"name":"Department of Pathology Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela C","family":"Salles","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adina","family":"Paulk","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1839-6472","authenticated-orcid":false,"given":"Jonathan I","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R","family":"Eshleman","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-9067","authenticated-orcid":false,"given":"Tamara L","family":"Lotan","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"WHO Classification of Tumours of the Urinary System and Male Genital Organs","author":"Moch H","year":"2016"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.236"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2017.12.003"},{"key":"e_1_2_8_5_1","article-title":"Genomic characterization of prostatic ductal adenocarcinoma identifies a high prevalence of DNA repair gene mutations","volume":"3","author":"Schweizer MT","year":"2019","journal-title":"JCO Precis. 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