Primary renal well-differentiated neuroendocrine tumour (carcinoid): next-generation sequencing study of 11 cases
Language English Country England, Great Britain Media print
Document type Case Reports, Journal Article
Grant support
Q39
Charles University Research Fund
FN 00669806
Charles University Research Fund
PubMed
30851202
DOI
10.1111/his.13856
Knihovny.cz E-resources
- Keywords
- carcinoid, kidney, next-generation sequencing, primary, well-differentiated neuroendocrine tumour,
- MeSH
- Cell Differentiation MeSH
- Antigens, CD genetics MeSH
- Dioxygenases MeSH
- DNA-Binding Proteins genetics MeSH
- Adult MeSH
- Immunohistochemistry MeSH
- Cadherins genetics MeSH
- Carcinoid Tumor genetics metabolism pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation MeSH
- Biomarkers, Tumor genetics metabolism MeSH
- Kidney Neoplasms genetics metabolism pathology MeSH
- Neuroendocrine Tumors genetics metabolism pathology MeSH
- Proto-Oncogene Proteins genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Loss of Heterozygosity MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Names of Substances
- Antigens, CD MeSH
- CDH1 protein, human MeSH Browser
- Dioxygenases MeSH
- DNA-Binding Proteins MeSH
- Cadherins MeSH
- Biomarkers, Tumor MeSH
- Proto-Oncogene Proteins MeSH
- TET2 protein, human MeSH Browser
AIMS: Primary renal well-differentiated neuroendocrine tumour (NET) (hereafter referred to as renal NET) is rare, with ~100 cases having been reported in the literature. There are also limited data on the molecular-genetic background of primary renal NETs. METHODS AND RESULTS: We analysed 11 renal NETs by using next-generation sequencing (NGS) to identify characteristic genetic aberrations. All tumours were positive for synaptophysin, and also expressed insulinoma-associated protein 1 (10/11), chromogranin-A (8/11), and CD56 (3/11). Cytoplasmic positivity of CD99 was present in eight of 11 cases, and strong nuclear expression of α-thalassaemia/mental retardation syndrome X-linked (ATRX) was retained in all 11 cases. Molecular-genetic analysis of aberration of VHL gave negative results in all cases. Loss of heterozygosity on chromosome 3p21 was found in three of nine analysable cases. NGS was successful in nine cases, showing a total of 56 variants being left after the updated filtering process, representing an average of five variants per sample. All analysable cases were negative for ATRX and DAXX (death-domain associated protein X) mutations. The most frequently mutated genes were CDH1 and TET2, with three mutations in two cases. Mutations in AKT3, ROS1, PIK3R2, BCR and MYC were found in two cases. The remaining 41 genes were found to be mutated only in individual cases. In four cases, the mutations affected a subset of genes related to angiogenesis. CONCLUSIONS: Overall, the mutation profile of primary renal NETs is variable, and none of the studied genes or affected pathways seems to be specific for renal NET.
Department of Diagnostic Pathology Kochi Red Cross Hospital Kochi Japan
Department of Pathology Central Military Hospital Prague Prague Czech Republic
Department of Pathology Centro Medico Mexico City Mexico
Department of Pathology Cytopathos Bratislava Slovakia
Department of Pathology Faculty of Medicine in Plzen Charles University Prague Pilsen Czech Republic
Department of Pathology INCAN Mexico City Mexico
Department of Pathology Regional Hospital Havirov Havirov Czech Republic
Department of Pathology School of Medicine Zagreb Croatia
Department of Pathology University of Erlangen Erlangen Germany
Department of Pathology Wojewódzki Szpital Specjalistyczny Wroclaw Poland
Department of Urology Faculty of Medicine in Plzeň Charles University Prague Pilsen Czech Republic
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