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PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included <jats:italic>KRAS<\/jats:italic> (38\u2013100%), <jats:italic>GNAS<\/jats:italic> (17\u2013100%), and <jats:italic>TP53<\/jats:italic> (5\u201323%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target <jats:italic>KRAS<\/jats:italic> and <jats:italic>GNAS<\/jats:italic> mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s10555-023-10088-0","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T06:04:05Z","timestamp":1675231445000},"page":"335-359","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The genetic profile and molecular subtypes of human pseudomyxoma peritonei and appendiceal mucinous neoplasms: a systematic review"],"prefix":"10.1007","volume":"42","author":[{"given":"Nora Wangari","family":"Murage","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada Mabrouk","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Underwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00eb S.","family":"Walters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-3187","authenticated-orcid":false,"given":"Stella Panagio","family":"Breininger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"issue":"2","key":"10088_CR1","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.ejso.2007.04.002","volume":"34","author":"R Smeenk","year":"2008","unstructured":"Smeenk, R., Van Velthuysen, M., Verwaal, V., et al. 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