Genomic profile of pseudomyxoma peritonei analyzed using next‐generation sequencing and immunohistochemistry. Issue 5 (13th October 2014)

• Record Type: Journal Article
• Authors: Nummela, Pirjo; Saarinen, Lilli; Thiel, Alexandra; Järvinen, Petrus; Lehtonen, Rainer; Lepistö, Anna; Järvinen, Heikki; Aaltonen, Lauri A; Hautaniemi, Sampsa; Ristimäki, Ari
• Is Part Of: International journal of cancer. Volume 136:Issue 5(2015:Mar. 01)
• Page Start: E282
• Page End: E289
• Publication Date: 2014-10-13
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29245
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <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‐investigated disease. We extracted DNA from 19 appendix‐derived PMP tumors and nine corresponding normal tissues, and analyzed the mutational hotspot areas of 48 cancer‐related genes by amplicon‐based next‐generation sequencing (NGS). Further, we analyzed the protein expression of V600E mutated BRAF, MLH1, MSH2, MSH6 and p53 from a larger set of PMP tumors (<italic>n</italic> = 74) using immunohistochemistry. With NGS, we detected activating somatic <italic>KRAS</italic> mutations in all of the tumors studied. <italic>GNAS</italic> was mutated in 63% of the tumors with no marked difference between low‐grade and high‐grade tumors. Only one (5.3%) tumor showed oncogenic <italic>PIK3CA</italic> mutation, one showed oncogenic <italic>AKT1</italic> mutation, three (15.8%) showed <italic>SMAD4</italic> mutations and none showed an <italic>APC</italic> mutation. P53 protein was aberrantly expressed in higher proportion of high‐grade tumors as compared with low‐grade ones (31.3 <italic>vs</italic>. 7.1%, respectively; <italic>p</italic> = 0.012) and aberrant expression was an independent factor for reduced overall survival (<italic>p</italic> = 0.002). <italic>BRAF</italic> V600E mutation was only found in one (1.4%) high‐grade tumor by immunohistochemistry (<italic>n</italic> = 74). All the studied tumors expressed mismatch repair proteins MLH1, MSH2 and MSH6. Our results indicate that <italic>KRAS</italic> mutations are evident in all and <italic>GNAS</italic> mutations in most of the PMPs, but <italic>BRAF</italic> V600E, <italic>PIK3CA</italic> and <italic>APC</italic> mutations are rare. Aberrantly expressed p53 is associated with high‐grade histology and reduced survival.</p> </abstract>