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MNA is often diagnosed after metastasis to the peritoneal surfaces resulting in mucinous carcinomatosis peritonei (MCP). Genetic alterations in MNA are poorly characterized due to its low incidence, the hypo-cellularity of MCPs, and a lack of relevant pre-clinical models. As such, application of targeted therapies to this disease is limited to those developed for colorectal cancer and not based on molecular rationale.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We sequenced the whole exomes of 10 MCPs of appendiceal origin to identify genome-wide somatic mutations and copy number aberrations and validated significant findings in 19 additional cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study demonstrates that MNA has a different molecular makeup than colorectal cancer. Most tumors have co-existing oncogenic mutations in\n                      <jats:italic>KRAS<\/jats:italic>\n                      (26\/29) and\n                      <jats:italic>GNAS<\/jats:italic>\n                      (20\/29) and are characterized by downstream PKA activation. High-grade tumors are\n                      <jats:italic>GNAS<\/jats:italic>\n                      wild-type (5\/6), suggesting they do not progress from low-grade tumors. MNAs do share some genetic alterations with colorectal cancer including gain of 1q (5\/10), Wnt, and TGF\u03b2 pathway alterations. In contrast, mutations in\n                      <jats:italic>TP53<\/jats:italic>\n                      (1\/10) and\n                      <jats:italic>APC<\/jats:italic>\n                      (0\/10), common in colorectal cancer, are rare in MNA. Concurrent activation of the\n                      <jats:italic>KRAS<\/jats:italic>\n                      and\n                      <jats:italic>GNAS<\/jats:italic>\n                      mediated signaling pathways appears to be shared with pancreatic intraductal papillary mucinous neoplasm.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MNA genome-wide mutational analysis reveals genetic alterations distinct from colorectal cancer, in support of its unique pathophysiology and suggests new targeted therapeutic opportunities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/gm559","type":"journal-article","created":{"date-parts":[[2014,5,29]],"date-time":"2014-05-29T07:02:56Z","timestamp":1401346976000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Genome-wide mutational landscape of mucinous carcinomatosis peritonei of appendiceal origin"],"prefix":"10.1186","volume":"6","author":[{"given":"Hakan","family":"Alakus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele L","family":"Babicky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradipta","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Yost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Jepsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L","family":"Samuels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangeline S","family":"Mose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M","family":"Lowy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A","family":"Frazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Harismendy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,5,29]]},"reference":[{"key":"536_CR1","doi-asserted-by":"publisher","first-page":"3307","DOI":"10.1002\/cncr.10589","volume":"94","author":"ME McCusker","year":"2002","unstructured":"McCusker ME, Cote TR, Clegg LX, Sobin LH: Primary malignant neoplasms of the appendix: a population-based study from the surveillance, epidemiology and end-results program, 1973-1998. 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