{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:18:50Z","timestamp":1790731130978,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Low\u2010grade appendiceal mucinous neoplasia (LAMN) represents a relatively rare tumor of the appendix typically diagnosed incidentally through appendectomy for acute appendicitis. In cases where perforation occurs, mucinous content may disseminate into the abdominal cavity, leading to the development of pseudomyxoma peritonei (PMP). The primary objective of this study was to elucidate the molecular characteristics associated with various stages of LAMN and PMP. DNA was extracted from LAMN, primary PMPs, recurrent PMPs, and adenocarcinomas originating from LAMN. The subsequent analysis involved the examination of mutational hotspot regions within 50 cancer\u2010related genes, covering over 2800 COSMIC mutations, utilizing amplicon\u2010based next\u2010generation sequencing (NGS). Our findings revealed activating somatic mutations within the MAPK\u2010signaling pathway across all tumors examined. Specifically, 98.1% of cases showed mutations in\n                    <jats:italic>KRAS<\/jats:italic>\n                    , while one tumor harbored a\n                    <jats:italic>BRAF<\/jats:italic>\n                    mutation. Additionally,\n                    <jats:italic>GNAS<\/jats:italic>\n                    mutations were identified in 55.8% of tumors, with no significant difference observed between LAMN and PMP. While LAMN rarely displayed additional mutations, 42% of primary PMPs and 60% of recurrent PMPs showed additional mutations. Notably, both adenocarcinomas originating from LAMN showed mutations within\n                    <jats:italic>TP53<\/jats:italic>\n                    . Furthermore, 7.7% (4\/52) of cases exhibited a potentially targetable\n                    <jats:italic>KRAS<\/jats:italic>\n                    G12C mutation. In four patients, NGS analysis was performed on both primary PMP and recurrent PMP\/adenocarcinoma samples. While mutations in\n                    <jats:italic>KRAS<\/jats:italic>\n                    and\n                    <jats:italic>GNAS<\/jats:italic>\n                    were detected in almost all samples, 50% of recurrent cases displayed an additional\n                    <jats:italic>SMAD4<\/jats:italic>\n                    mutation, suggesting a notable alteration during disease progression. Our findings indicate two key points: First, mutations within the MAPK pathway, particularly in\n                    <jats:italic>KRAS<\/jats:italic>\n                    , are evident across all tumors, along with a high frequency of\n                    <jats:italic>GNAS<\/jats:italic>\n                    mutations. Second, progression toward PMP or adenocarcinoma is associated with an accumulation of additional mutations within common oncogenic pathways.\n                  <\/jats:p>","DOI":"10.1002\/gcc.23270","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T08:23:26Z","timestamp":1728894206000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Molecular Profiling of Low\u2010Grade Appendiceal Mucinous Neoplasms (\n                    <scp>LAMN<\/scp>\n                    )"],"prefix":"10.1002","volume":"63","author":[{"given":"Julia","family":"Doll","sequence":"first","affiliation":[{"name":"Institute of Pathology University of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Comprehensive Cancer Center Mainfranken University of W\u00fcrzburg Medical Centre  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Maurus","sequence":"additional","affiliation":[{"name":"Institute of Pathology University of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Comprehensive Cancer Center Mainfranken University of W\u00fcrzburg Medical Centre  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery University Hospital, University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Matthes","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery University Hospital, University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan F.","family":"Lock","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery University Hospital, University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph\u2010Thomas","family":"Germer","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Mainfranken University of W\u00fcrzburg Medical Centre  W\u00fcrzburg Germany"},{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery University Hospital, University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Rosenwald","sequence":"additional","affiliation":[{"name":"Institute of Pathology University of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Comprehensive Cancer Center Mainfranken University of W\u00fcrzburg Medical Centre  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7777-0909","authenticated-orcid":false,"given":"Armin","family":"Wiegering","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Mainfranken University of W\u00fcrzburg Medical Centre  W\u00fcrzburg Germany"},{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery University Hospital, University of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Department of Biochemistry and Molecular Biology University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"519","article-title":"Neoplasms of the Appendix","volume":"120","author":"Kohler F.","year":"2023","journal-title":"Deutsches \u00c4rzteblatt International"},{"key":"e_1_2_9_3_1","article-title":"Low\u2010Grade Appendiceal Mucinous Neoplasm: What Is the Best Treatment?","volume":"15","author":"Guner 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Chromosomes and 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