{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:55:03Z","timestamp":1790430903537,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,9,17]],"date-time":"2009-09-17T00:00:00Z","timestamp":1253145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A candidate early precursor to pelvic serous cancer, the \u2018p53 signature\u2019, is commonly found in the benign mucosa of the distal Fallopian tube and harbours <jats:italic>p53<\/jats:italic> mutations and evidence of DNA damage. We examined tubes from women with pre\u2010existing (germ\u2010line) mutations in <jats:italic>p53<\/jats:italic> [Li\u2013Fraumeni syndrome (LFS)] for evidence of this precursor. Fallopian tubes from two cases of LFS were immunostained for p53, Ki\u201067 (proliferation) and H2AX (DNA damage response) and analysed for <jats:italic>p53<\/jats:italic> mutations by laser capture microdissection (LCM) and <jats:italic>p53<\/jats:italic> genomic sequencing (exons 2\u201311). A common single nucleotide repeat (snp) in exon 3 (rs1042522) and deletion sequencing chromatograms in exon 4 were examined in combination to estimate LOH in both LFS tubes and advanced serous carcinomas from the general population. LFS tubal epithelium contained abundant (10\u201320 per section) p53 signatures with evidence of DNA damage and low proliferative activity. Six of 11 LFS microdissected p53 signatures (55%) and 15 of 21 serous carcinomas (71%) revealed LOH at the <jats:italic>p53<\/jats:italic> locus, relative to background epithelium. The LFS model confirms prior observations that the distal Fallopian tube is particularly prone to focal epithelial <jats:italic>p53<\/jats:italic> gene inactivation\u2014<jats:italic>p53<\/jats:italic> mutation and LOH\u2014in the absence of malignancy or increased epithelial proliferation. The fact that the LFS is <jats:italic>not<\/jats:italic> associated with ovarian cancers is consistent with the concept that loss of p53 function must be accompanied by at least one more genotoxic event (including BRCA1\/2 functional inactivation) to produce the malignant phenotype. This is in keeping with a general model of carcinogenesis, in which different and often independent risk factors operate at multiple points in the serous carcinogenic spectrum. Copyright \u00a9 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2624","type":"journal-article","created":{"date-parts":[[2009,9,17]],"date-time":"2009-09-17T10:07:11Z","timestamp":1253182031000},"page":"17-23","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["The Li\u2013Fraumeni syndrome (LFS): a model for the initiation of p53 signatures in the distal Fallopian tube"],"prefix":"10.1002","volume":"220","author":[{"given":"Wa","family":"Xian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Miron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Roh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana 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