Molecular and clinicopathological features of appendiceal mucinous neoplasms
Autor: | Ryo Wada, Takuo Hayashi, Yuka Yanai, Shigeki Tomita, Sho Tsuyama, Kanako Ogura, Yoichi Akazawa, Toshiharu Matsumoto, Takashi Yao, Noboru Yatagai, Shu Hirai, Tsuyoshi Saito |
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Rok vydání: | 2020 |
Předmět: |
Adult
Male 0301 basic medicine Ubiquitin-Protein Ligases DNA Mutational Analysis Loss of Heterozygosity medicine.disease_cause Tp53 mutation Pathology and Forensic Medicine Proto-Oncogene Proteins p21(ras) Young Adult 03 medical and health sciences symbols.namesake 0302 clinical medicine Biomarkers Tumor Chromogranins GTP-Binding Protein alpha Subunits Gs medicine GNAS complex locus Humans Pseudomyxoma peritonei Missense mutation Tokyo Molecular Biology Aged Neoplasm Staging Aged 80 and over Sanger sequencing biology High-Throughput Nucleotide Sequencing Cell Biology General Medicine Middle Aged medicine.disease Adenocarcinoma Mucinous Immunohistochemistry Mucinous Adenocarcinomas 030104 developmental biology Appendiceal Neoplasms 030220 oncology & carcinogenesis Mutation Cancer research biology.protein symbols Clinicopathological features Female KRAS Neoplasm Grading Tumor Suppressor Protein p53 |
Zdroj: | Virchows Archiv. 478:413-426 |
ISSN: | 1432-2307 0945-6317 |
Popis: | Appendiceal mucinous tumors (AMTs) include low-grade mucinous appendiceal neoplasms (LAMNs), high-grade mucinous appendiceal neoplasms (HAMNs), and mucinous adenocarcinomas (MACs). We collected 51 AMT samples (LAMN: 34, HAMN: 8, MAC: 9). Three of the eight HAMN cases contained LAMN components, and four out of nine MAC cases contained LAMN and/or HAMN components within the tumor. A next-generation sequencing (NGS) cancer hotspot panel was used to analyze 11 pure LAMN, 4 HAMN, and 3 MAC cases. The results revealed KRAS and GNAS as the most frequently mutated genes. Sanger sequencing was then performed to detect KRAS, GNAS, and TP53 mutations in the remaining 31 cases and RNF43 mutations in all cases. KRAS/GNAS and TP53 mutations occurred exclusively in pure LAMNs; however, five LAMN cases had mutations in both KRAS and GNAS. RNF43 mutations almost exclusively occurred with KRAS/GNAS mutations in pure LAMNs. In MAC and HAMN, KRAS/GNAS mutation status was nearly preserved between lower-grade areas. Most of the detected RNF43 mutations was missense type. RNF43 mutations were detected in both components of MAC with lower-grade area; however, RNF43 mutations detected in these two lesions were entirely different. RNF43 mutations were detected in only one of the eight HAMN patients, which was the sole case without pseudomyxoma peritonei (PMP). None of the four MAC patients with RNF43 mutation showed PMP. These findings suggest that RNF43 mutations occur at a later stage of MAC development and do not associate with PMP. Furthermore, a gradual transition from LAMN to MAC via HAMN could be considered. |
Databáze: | OpenAIRE |
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