CTNNB1 mutational analysis of solid-pseudopapillary neoplasms of the pancreas using endoscopic ultrasound-guided fine-needle aspiration and next-generation deep sequencing

Kubota, Yoshimasa; Kawakami, Hiroshi; Natsuizaka, Mitsuteru; Kawakubo, Kazumichi; Marukawa, Katsuji; Kudo, Taiki; Abe, Yoko; Kubo, Kimitoshi; Kuwatani, Masaki; Hatanaka, Yutaka; Mitsuhashi, Tomoko; Matsuno, Yoshihiro; Sakamoto, Naoya

doi:10.1007/s00535-014-0954-y

Cited by 34 publications

(32 citation statements)

References 32 publications

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“…EUS-FNA demonstrates high sensitivity for histological diagnosis (75–94%) and a specificity approaching 100% in the majority of studies (5,6). However, false-negative, atypical and suspicious cytopathological diagnoses remain relatively frequent (5,7,8). …”

Section: Introductionmentioning

confidence: 99%

Diagnosis of pancreatic lesions collected by endoscopic ultrasound-guided fine-needle aspiration using next-generation sequencing

et al. 2016

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Endoscopic ultrasound-guided fine-needle aspiration (EUF-FNA) has improved the diagnosis of pancreatic lesions. Next-generation sequencing (NGS) facilitates the production of millions of sequences concurrently. Therefore, in the current study, to improve the detectability of oncogenic mutations in pancreatic lesions, an NGS system was used to diagnose EUS-FNA samples. A total of 38 patients with clinically diagnosed EUS-FNA specimens were analyzed; 27 patients had pancreatic ductal adenocarcinoma (PDAC) and 11 had non-PDAC lesions. DNA samples were isolated and sequenced by NGS using an Ion Personal Genome Machine system. The Cancer Hotspot Panel v2, which includes 50 cancer-related genes and 2,790 COSMIC mutations, was used. A >2% mutation frequency was defined as positive. KRAS mutations were detected in 26 of 27 PDAC aspirates (96%) and 0 of 11 non-PDAC lesions (0%). The G12, G13, and Q61 KRAS mutations were found in 25, 0, and 1 of the 27 PDAC samples, respectively. Mutations were confirmed by TaqMan® polymerase chain reaction analysis. TP53 mutations were detected in 12 of 27 PDAC aspirates (44%). SMAD4 was observed in 3 PDAC lesions and cyclin-dependent kinase inhibitor 2A in 4 PDAC lesions. Therefore, the current study was successfully able to develop an NGS assay with high clinical sensitivity for EUS-FNA samples.

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Section: Introductionmentioning

confidence: 99%

Diagnosis of pancreatic lesions collected by endoscopic ultrasound-guided fine-needle aspiration using next-generation sequencing

et al. 2016

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“…Therefore, different NGS platforms use FNC to harvest cells from different tumors [92,93,94,95,96,97,98,99,100]. These studies demonstrated that NGS-based mutational profiling can be performed with a few nanograms of DNA (∼40 ng/μl), which can be easily obtained from FNC in different tumors [93,94,95,96,97,98]. Therefore, NGS may enhance the molecular FNC potential, providing mutational information on genes with high diagnostic and predictive relevance, such as EGFR, BRAF, K/N/HRAS, KIT, PTEN, CDKN2A, just to mention some, thus contributing to personalized therapies.…”

Section: High-throughput Technologies-based Arraysmentioning

confidence: 99%

Lymph Node Fine-Needle Cytology: Beyond Flow Cytometry

Peluso

Ieni²,

Mignogna³

et al. 2016

Acta Cytologica

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Lymph node (LN) fine-needle cytology (FNC) coupled with flow cytometry immunophenotyping provides relevant information for the diagnosis of non-Hodgkin lymphoma (NHL). Numerous studies have shown FNC samples to be suitable for different molecular procedures; in this review, some of the molecular procedures most commonly employed for NHL are briefly described and evaluated in this perspective. Fluorescence in situ hybridization and chromogenic in situ hybridization are briefly described. Polymerase chain reaction (PCR)-based assays are used to identify and quantify mutations and translocations, namely immunoglobulin (IGH) and T-cell receptor rearrangements by clonality testing and IGVH somatic hypermutations either by Sanger sequencing, single-strand conformational polymorphisms or RT-PCR strategies. High-throughput technologies (HTT) encompass numerous and different diagnostic tools that share the capacity of multiple molecular investigation and sample processing in a fast and reproducible manner. HTT includes gene expression profiling, comparative genomic hybridization, single-nucleotide polymorphism arrays and next-generation sequencing technologies. A brief description of these tools and their potential application to LN FNC is reported. The challenge for FNC will be to achieve new knowledge and apply new technologies to FNC, exploiting its own basic qualities.

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“…There have been previous studies using next generation sequencing to analyze SPNs of the pancreas. However, in all these reports, the SPNs showed recurrent pathogenic variants only in the CTNNB1 gene …”

Section: Discussionmentioning

confidence: 93%

Targeted next generation sequencing of pancreatic solid pseudopapillary neoplasms show mutations in Wnt signaling pathway genes

Wang

Gerrard

Poskitt

et al. 2019

Pathology International

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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.

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CTNNB1 mutational analysis of solid-pseudopapillary neoplasms of the pancreas using endoscopic ultrasound-guided fine-needle aspiration and next-generation deep sequencing

Abstract: Background: Solid-pseudopapillary neoplasm (SPN), a rare neoplasm of the pancreas,

Cited by 34 publications

References 32 publications

Diagnosis of pancreatic lesions collected by endoscopic ultrasound-guided fine-needle aspiration using next-generation sequencing

Diagnosis of pancreatic lesions collected by endoscopic ultrasound-guided fine-needle aspiration using next-generation sequencing

Lymph Node Fine-Needle Cytology: Beyond Flow Cytometry

Targeted next generation sequencing of pancreatic solid pseudopapillary neoplasms show mutations in Wnt signaling pathway genes

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