Feasibility and clinical utility of EUS guided biopsy of pancreatic cancer for next-generation genomic sequencing.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15755-e15755
Author(s):  
Stephan Dreyer ◽  
Nigel Jamieson ◽  
Lisa Evers ◽  
Marc Jones ◽  
Sancha Martin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Rna Sequencing ◽  
Clinical Utility ◽  
Frozen Section ◽  
Brca1 Mutation ◽  
Resected Specimen ◽  
Genomic Profiling ◽  
Next Generation ◽  
Fresh Frozen ◽  
Panel Sequencing

e15755 Background: Next-generation sequencing (NGS) has made genomic profiling to guide therapy a reality for many cancer types. The aim of this study is to investigate the feasibility of genomic profiling using standard clinical endoscopic ultrasound (EUS) core biopsy samples of Pancreatic Cancer (PC) to allow personalised cancer care. Methods:Patients undergoing EUS and biopsy for suspicion of PC underwent additional biopsies which was snap frozen. En-face frozen section enabled targeted macro-dissection prior to DNA extraction, quantification and targeted sequencing using a commercially available 151 gene ClearSeq Comprehensive Cancer Panel. Matching formalin-fixed (FFPE) diagnostic EUS biopsy and fresh frozen surgical resection specimens underwent genomic profiling for comparison. Whole genome sequencing (WGS) was performed in 2 patients. RNA sequencing was performed in samples with sufficient RNA yield. Results: Known PC genes ( KRAS, GNAS, TP53, CDKN2A, SMAD4) were identified in 27 out of 30 (90%) patients with histological diagnosis of PC. Potentially actionable somatic mutations (BRCA1, BRCA2, ATM, BRAF, JAK3) were found in 6 (20%) patients. In the 2 samples selected, WGS of the EUS samples confirmed point mutations identified on panel sequencing and revealed relevant mutational signatures and structural variation patterns. Targeted panel sequencing was successful in all FFPE samples. In 1 chemotherapy naïve patient, sequencing of a matching trio of fresh frozen and FFPE EUS biopsies, and resection sample revealed evidence of spatial intra-tumoral heterogeneity. In another patient, pre-treatment biopsy revealed a somatic BRCA1 mutation, and patient had a near complete pathological response to platinum containing neoadjuvant therapy in the resected specimen. RNA sequencing segregated patients into key clinically relevant molecular PC subtypes based on transcriptome as recently described. Conclusions: We demonstrate here novel multi-omic analysis of pancreatic cancer using standard clinical EUS guided fine needle biopsies. Multi-omic analysis of EUS biopsies offers potential clinical utility to guide personalized therapy of PC in the neoadjuvant and advanced settings.

Feasibility and clinical utility of EUS guided biopsy of pancreatic cancer for next-generation genomic sequencing.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 296-296 ◽  
Author(s):  
Stephan Dreyer ◽  
Nigel Jamieson ◽  
Lisa Evers ◽  
Marc Jones ◽  
Sancha Martin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Rna Sequencing ◽  
Clinical Utility ◽  
Frozen Section ◽  
Genomic Profiling ◽  
Next Generation ◽  
Next Generation Sequencing Technology ◽  
Fresh Frozen ◽  
Targeted Gene Sequencing ◽  
Panel Sequencing

296 Background: Next-generation sequencing technology has made genomic profiling guided therapy a reality for many cancer types. The aim of this study is to investigate the feasibility of genomic profiling using standard clinical endoscopic ultrasound (EUS) core biopsy samples of Pancreatic Cancer (PC) to allow personalised cancer care. Methods: 78 patients underwent additional research biopsy at the time of diagnostic EUS biopsy. En-face frozen section was performed to enable targeted macro-dissection prior to DNA extraction, quantification and targeted gene sequencing (Agilent Comprehensive Cancer Gene Panel). Matching formalin-fixed (FFPE) diagnostic EUS biopsies and fresh frozen surgical resection specimens also underwent genomic profiling for comparison. Whole genome (WGS) and RNA sequencing was performed in selected patients. Results: Targeted panel sequencing ( n = 61) revealed known PC genes ( KRAS, GNAS, TP53, CDKN2A, SMAD4) in 36 patients with histological evidence of PC. Potentially actionable somatic mutations (BRCA1, BRCA2, ATM, BRAF, JAK3) were found in 6 (17%) patients. WGS ( n = 5) of EUS samples confirmed mutations identified on panel sequencing and revealed relevant mutational signatures and structural variation patterns that can act as putative biomarkers of therapeutic responsiveness. RNA sequencing ( n = 54) segregated patients into key clinically relevant molecular PC subtypes based on transcriptome and reveals novel molecular insights into advanced, unresectable PC ( n = 38). Conclusions: We demonstrate here novel multi-omic analysis of pancreatic cancer using standard clinical EUS guided fine needle biopsies. Multi-omic analysis of EUS biopsies offers potential clinical utility to guide personalized therapy of PC in both the neoadjuvant and advanced settings.

Mo1389 – Detection System of Circulating Tumor Dna for Pancreatic Cancer Using Next-Generation Sequencing and Its Clinical Utility

2019 ◽  
Vol 156 (6) ◽  
pp. S-760
Author(s):  
Kazuyoshi Ohkawa ◽  
Ryoji Takada ◽  
Kenji Ikezawa ◽  
Nobuyasu Fukutake ◽  
Abe Yutaro ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Next Generation Sequencing ◽  
Clinical Utility ◽  
Detection System ◽  
Circulating Tumor Dna ◽  
Next Generation ◽  
Tumor Dna ◽  
Generation Sequencing

scholarly journals MO31-3 Intratumor microbiome analysis of pancreatic cancer by analyzing the fresh frozen tissues obtained by EUS-FNA

2021 ◽  
Vol 32 ◽  
pp. S318
Author(s):  
Shintaro Nakano ◽  
Yasuyuki Kawamoto ◽  
Kazuaki Harada ◽  
Ken Ito ◽  
Rika Saito ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Microbiome Analysis ◽  
Fresh Frozen

scholarly journals Suitability of Bronchoscopic Biopsy Tissue Samples for Next-Generation Sequencing

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 391
Author(s):  
Shuji Murakami ◽  
Tomoyuki Yokose ◽  
Daiji Nemoto ◽  
Masaki Suzuki ◽  
Ryou Usui ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Success Rate ◽  
Rna Sequencing ◽  
Surface Area ◽  
Endobronchial Ultrasound ◽  
Next Generation ◽  
Endobronchial Ultrasonography ◽  
Tissue Surface ◽  
The Impact ◽  
Generation Sequencing

A sufficiently large tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥1 mm2) and tumor content rate (≥30%) on the success rate of the Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

scholarly journals Clinical utility of comprehensive genomic profiling in central nervous system tumors of children and young adults

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Jianling Ji ◽  
Kristiyana Kaneva ◽  
Matthew C Hiemenz ◽  
Girish Dhall ◽  
Tom Belle Davidson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Utility ◽  
Adolescent And Young Adult ◽  
Cns Tumors ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Genomic Profiling ◽  
Comprehensive Genomic Profiling ◽  
Clinically Significant

Abstract Background Recent large-scale genomic studies have revealed a spectrum of genetic variants associated with specific subtypes of central nervous system (CNS) tumors. The aim of this study was to determine the clinical utility of comprehensive genomic profiling of pediatric, adolescent and young adult (AYA) CNS tumors in a prospective setting, including detection of DNA sequence variants, gene fusions, copy number alterations (CNAs), and loss of heterozygosity. Methods OncoKids, a comprehensive DNA- and RNA-based next-generation sequencing (NGS) panel, in conjunction with chromosomal microarray analysis (CMA) was employed to detect diagnostic, prognostic, and therapeutic markers. NGS was performed on 222 specimens from 212 patients. Clinical CMA data were analyzed in parallel for 66% (146/222) of cases. Results NGS demonstrated clinically significant alterations in 66% (147/222) of cases. Diagnostic markers were identified in 62% (138/222) of cases. Prognostic information and targetable genomic alterations were identified in 22% (49/222) and 18% (41/222) of cases, respectively. Diagnostic or prognostic CNAs were revealed by CMA in 69% (101/146) of cases. Importantly, clinically significant CNAs were detected in 57% (34/60) of cases with noncontributory NGS results. Germline cancer predisposition testing was indicated for 27% (57/212) of patients. Follow-up germline testing was performed for 20 patients which confirmed a germline pathogenic/likely pathogenic variant in 9 cases: TP53 (2), NF1 (2), SMARCB1 (1), NF2 (1), MSH6 (1), PMS2 (1), and a patient with 47,XXY Klinefelter syndrome. Conclusions Our results demonstrate the significant clinical utility of integrating genomic profiling into routine clinical testing for pediatric and AYA patients with CNS tumors.

Sign in / Sign up

Export Citation Format

Share Document