Next-Generation Sequencing Analysis of Pancreatic Cancer Using Residual Liquid Cytology Specimens from Endoscopic Ultrasound—Guided Fine-Needle Biopsy: A Prospective Comparative Study with Tissue Specimens

Abstract

This study evaluated the feasibility and clinical utility of liquid-based cytology (LBC) specimens via endoscopic ultrasound–guided fine-needle biopsy (EUS-FNB) for next-generation sequencing (NGS) of pancreatic cancer (PC). We prospectively evaluated the performance of DNA extraction and NGS using EUS-FNB samples obtained from PC. Thirty-three consecutive patients with PC who underwent EUS-FNB at our hospital were enrolled. DNA samples were obtained from 96.8% of the patients. When stratified with a variant allele frequency (VAF) > 10% tumor burden, the NGS success rate was 76.7% (n = 23) in formalin-fixed paraffin-embedded (FFPE), 83.3% (n = 25) in LBC, and 76.7% (n = 23) in frozen samples. The overall NGS success rate was 86.7% (n = 26) using FFPE, LBC, or frozen samples. The detection rates for the main mutated genes were as follows: 86.7% for KRAS, 73.3% for TP53, 66.7% for CDKN2A, 36.7% for SMAD4, and 16.7% for ARID1A. LBC had the highest median value of VAF (23.5%) for KRAS and TP53. PC mutation analysis using NGS was successfully performed using LBC compared with FFPE and frozen samples. This approach provides an alternative and affordable source of molecular testing materials.

Molecular underpinnings of pancreatic cancer: Innovations in treatment and future perspectives

“…[6] With the advent of next-generation sequencing (NGS), we have gained a better understanding of the genomic landscape of PDAC, revealing less commonly changed genes that play unique roles in distinct subtypes of cancers. [7,8] Some PDAC patients have germline mutations in genes such BRCA1, BRCA2, and PALB2, making them vulnerable to PARP inhibitors and platinum-based treatments. [9] Chromatin-remodeling and SWI/SNF complex genes are frequently altered in PDAC and may exhibit context-dependent tumor-suppressor or oncogenic functions.…”

Next-generation sequencing on fine needle aspirates in neck recurrence of thyroid cancers

“…plasma samples, can also be performed, chiefly to search for somatic mutations ( 4 , 5 ). Molecular genotyping on fine needle aspirates can be used to infer the risk of malignancy in indeterminate thyroid nodules ( 6 , 7 , 8 ) and for genetic analysis in other types of cancers such as pancreatic cancers ( 9 ).…”