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
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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