Targeted next generation sequencing of pancreatic solid pseudopapillary neoplasms show mutations in Wnt signaling pathway genes.
Pathol Int
; 69(4): 193-201, 2019 Apr.
Article
en En
| MEDLINE
| ID: mdl-30811747
ABSTRACT
Solid pseudopapillary neoplasms of the pancreas are rare neoplasms that have been shown to harbor recurrent somatic pathogenic variants in the beta-catenin gene, CTNNB1. Here, we used targeted next generation sequencing to analyze these tumors for other associated mutations. Six cases of solid pseudopapillary neoplasms were studied. DNA extracted from formalin-fixed paraffin embedded tissue blocks was analyzed using the Ion Torrent platform, with the 50-gene Ampliseq Cancer Hotspot Panel v2 (CHPv2), with further variant validation performed by Sanger sequencing. Four tumors (67%) were confirmed to harbor mutations within CTNNB1, two with c.109T > G p.(Ser37Ala) and two with c.94G > A p.(Asp32Asn). One case showed a frameshift deletion in the Adenomatous Polyposis Coli gene, APC c.3964delG p.(Glu1322Lysfs*93) with a variant allele frequency of 42.6%. Sanger sequencing on non-tumoral tissue confirmed the variant was somatic. The patient with the APC mutation developed metastasis and died. In addition to the four cases harboring CTNNB1 variants, we found a case characterized by poor outcome, showing a rare frameshift deletion in the APC gene. Since the APC product interacts with beta-catenin, APC variants may, in addition to CTNNB1, contribute to the pathogenesis of solid pseudopapillary neoplasms via the Wnt signaling pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Neoplasias Glandulares y Epiteliales
/
Beta Catenina
/
Vía de Señalización Wnt
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Pathol Int
Asunto de la revista:
PATOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido