{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:28:14Z","timestamp":1792794494534,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,10,13]],"date-time":"2014-10-13T00:00:00Z","timestamp":1413158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"University of Helsinki, Sigrid Juselius Foundation, the Finnish Cancer Organizations and Helsinki University Central Hospital Research Funds"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:p>Pseudomyxoma peritonei (PMP) is a relatively rare clinical syndrome characterized by neoplastic epithelial cells growing in the peritoneal cavity and secreting mucinous ascites. Our aim was to explore the molecular events behind this fatal but under\u2010investigated disease. We extracted DNA from 19 appendix\u2010derived PMP tumors and nine corresponding normal tissues, and analyzed the mutational hotspot areas of 48 cancer\u2010related genes by amplicon\u2010based next\u2010generation sequencing (NGS). Further, we analyzed the protein expression of V600E mutated BRAF, MLH1, MSH2, MSH6 and p53 from a larger set of PMP tumors (<jats:italic>n<\/jats:italic>\u2009=\u200974) using immunohistochemistry. With NGS, we detected activating somatic <jats:italic>KRAS<\/jats:italic> mutations in all of the tumors studied. <jats:italic>GNAS<\/jats:italic> was mutated in 63% of the tumors with no marked difference between low\u2010grade and high\u2010grade tumors. Only one (5.3%) tumor showed oncogenic <jats:italic>PIK3CA<\/jats:italic> mutation, one showed oncogenic <jats:italic>AKT1<\/jats:italic> mutation, three (15.8%) showed <jats:italic>SMAD4<\/jats:italic> mutations and none showed an <jats:italic>APC<\/jats:italic> mutation. P53 protein was aberrantly expressed in higher proportion of high\u2010grade tumors as compared with low\u2010grade ones (31.3 <jats:italic>vs<\/jats:italic>. 7.1%, respectively; <jats:italic>p<\/jats:italic>\u2009=\u20090.012) and aberrant expression was an independent factor for reduced overall survival (<jats:italic>p<\/jats:italic>\u2009=\u20090.002). <jats:italic>BRAF<\/jats:italic> V600E mutation was only found in one (1.4%) high\u2010grade tumor by immunohistochemistry (<jats:italic>n<\/jats:italic>\u2009=\u200974). All the studied tumors expressed mismatch repair proteins MLH1, MSH2 and MSH6. Our results indicate that <jats:italic>KRAS<\/jats:italic> mutations are evident in all and <jats:italic>GNAS<\/jats:italic> mutations in most of the PMPs, but <jats:italic>BRAF<\/jats:italic> V600E, <jats:italic>PIK3CA<\/jats:italic> and <jats:italic>APC<\/jats:italic> mutations are rare. Aberrantly expressed p53 is associated with high\u2010grade histology and reduced survival.<\/jats:p>","DOI":"10.1002\/ijc.29245","type":"journal-article","created":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T16:17:28Z","timestamp":1412180248000},"source":"Crossref","is-referenced-by-count":77,"title":["Genomic profile of pseudomyxoma peritonei analyzed using next\u2010generation sequencing and immunohistochemistry"],"prefix":"10.1002","volume":"136","author":[{"given":"Pirjo","family":"Nummela","sequence":"first","affiliation":[{"name":"Genome\u2010Scale Biology Research Program, Research Programs Unit University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilli","family":"Saarinen","sequence":"additional","affiliation":[{"name":"Genome\u2010Scale Biology Research Program, Research Programs Unit University of Helsinki Helsinki 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