{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T20:34:55Z","timestamp":1778704495852,"version":"3.51.4"},"reference-count":41,"publisher":"Cold Spring Harbor Laboratory","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:p>Although the progressive histologic steps leading to endometrial cancer (EndoCA), the most common female reproductive tract malignancy, from endometrial hyperplasia are well-established, the molecular changes accompanying this malignant transformation in a single patient have never been described. We had the unique opportunity to investigate the paired histologic and molecular features associated with the 12-yr development of EndoCA in a postmenopausal female who could not undergo hysterectomy and instead underwent progesterone treatment. Using a specially designed 58-gene next-generation sequencing panel, we analyzed a total of 10 sequential biopsy samples collected over this time frame. A total of eight pathogenic\/likely pathogenic mutations in seven genes,<jats:italic>APC<\/jats:italic>,<jats:italic>ARID1A<\/jats:italic>,<jats:italic>CTNNB1<\/jats:italic>,<jats:italic>CDKN2A<\/jats:italic>,<jats:italic>KRAS<\/jats:italic>,<jats:italic>PTEN<\/jats:italic>, and<jats:italic>TP53<\/jats:italic>, were identified. A<jats:italic>PTEN<\/jats:italic>nonsense mutation p.W111* was present in all samples analyzed except histologically normal endometrium. Apart from this<jats:italic>PTEN<\/jats:italic>mutation, the only other recurrent mutation was<jats:italic>KRAS<\/jats:italic>G12D, which was present in six biopsy samplings, including histologically normal tissue obtained at the patient's first visit but not detectable in the cancer. The<jats:italic>PTEN<\/jats:italic>p.W111* mutant allele fractions were lowest in benign, inactive endometrial glands (0.7%), highest in adenocarcinoma (36.9%), and, notably, were always markedly reduced following progesterone treatment. To our knowledge, this report provides the first molecular characterization of EndoCA development in a single patient. A single<jats:italic>PTEN<\/jats:italic>mutation was present throughout the 12 years of cancer development. Importantly, and with potential significance toward medical and nonsurgical management of EndoCA, progesterone treatments were consistently noted to markedly decrease<jats:italic>PTEN<\/jats:italic>mutant allele fractions to precancerous levels.<\/jats:p>","DOI":"10.1101\/mcs.a006311","type":"journal-article","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T14:40:23Z","timestamp":1697553623000},"page":"a006311","source":"Crossref","is-referenced-by-count":1,"title":["Deep molecular tracking over the 12-yr development of endometrial cancer from hyperplasia in a single patient"],"prefix":"10.1101","volume":"9","author":[{"given":"Katherine","family":"Reid","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Camacho-Vanegas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deep","family":"Pandya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra Catalina","family":"Camacho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui Fang","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Kalir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria M.","family":"Padron-Rhenals","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Marie","family":"Beddoe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Dottino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Martignetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"246","published-online":{"date-parts":[[2023,10,17]]},"reference":[{"key":"2024011009350921000_9.4.a006311.1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21058"},{"key":"2024011009350921000_9.4.a006311.2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-8258(83)90111-7"},{"key":"2024011009350921000_9.4.a006311.3","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.247"},{"key":"2024011009350921000_9.4.a006311.4","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2018.6956"},{"key":"2024011009350921000_9.4.a006311.5","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000465189.50026.20"},{"key":"2024011009350921000_9.4.a006311.6","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-010-9612-8"},{"key":"2024011009350921000_9.4.a006311.7","first-page":"746856","article-title":"PTEN sequence analysis in endometrial hyperplasia and endometrial carcinoma in Slovak women","volume":"2015","year":"2015","journal-title":"Anal Cell Pathol (Amst)"},{"key":"2024011009350921000_9.4.a006311.8","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318212782a"},{"key":"2024011009350921000_9.4.a006311.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.08.029"},{"key":"2024011009350921000_9.4.a006311.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature09208"},{"key":"2024011009350921000_9.4.a006311.11","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1242998"},{"key":"2024011009350921000_9.4.a006311.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(01)00815-1"},{"key":"2024011009350921000_9.4.a006311.13","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19850715)56:2<403::AID-CNCR2820560233>3.0.CO;2-X"},{"key":"2024011009350921000_9.4.a006311.14","unstructured":"Kurman RJ , Carcangiu ML , Herrington CS , Young RH . 2014. 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