Molecular and clinicopathological features of appendiceal mucinous neoplasms.
Adenocarcinoma, Mucinous
/ chemistry
Adult
Aged
Aged, 80 and over
Appendiceal Neoplasms
/ chemistry
Biomarkers, Tumor
/ analysis
Chromogranins
/ genetics
DNA Mutational Analysis
Female
GTP-Binding Protein alpha Subunits, Gs
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Loss of Heterozygosity
Male
Middle Aged
Mutation
Neoplasm Grading
Neoplasm Staging
Proto-Oncogene Proteins p21(ras)
/ genetics
Tokyo
Tumor Suppressor Protein p53
/ genetics
Ubiquitin-Protein Ligases
/ genetics
Young Adult
Appendiceal mucinous tumor
GNAS
KRAS
Low-grade appendiceal mucinous neoplasm
Mucinous adenocarcinoma
Next-generation sequencing
RNF43
TP53
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
10
12
2019
accepted:
10
08
2020
revised:
27
07
2020
pubmed:
22
8
2020
medline:
31
3
2021
entrez:
22
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32821969
doi: 10.1007/s00428-020-02906-5
pii: 10.1007/s00428-020-02906-5
doi:
Substances chimiques
Biomarkers, Tumor
0
Chromogranins
0
KRAS protein, human
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
RNF43 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
GNAS protein, human
EC 3.6.1.-
GTP-Binding Protein alpha Subunits, Gs
EC 3.6.5.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Comparative Study
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
413-426Subventions
Organisme : Japan Agency for Medical Research and Development (JP)
ID : JP17am0001009
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