Dataset Information

Feasibility study of cancer genome alterations identified by next generation sequencing: ABC study.

ABSTRACT: To confirm the feasibility and explore the clinical applicability of amplicon sequencing by next generation sequencing (NGS) of biopsy samples from patients with advanced solid tumors, we conducted a prospective study.Patients with unresectable, advanced, or recurrent solid tumors were included. Key eligibility criteria were as follows: 20 years or older, any planned systemic therapy, adequate lesion for biopsy, and written informed consent. Samples were fixed in 10% buffered formalin and embedded in paraffin. Cancer-derived DNA was extracted, and amplicon sequencing was performed using Ion AmpliseqTM Cancer Hotspot Panel version 1.0 or version 2.0 by central vendor. We evaluated the success rate of sequencing, and the proportion of the patients with actionable mutations. We organized an expert panel to share the results of targeted sequence, make annotations and reports, and discuss concomitant ethical/legal/social issues.A total of 232 patients were included, and 208 were successfully analyzed (success rate of 89.7%). The biopsy procedures were safe, with only one case of Grade 3 vasovagal reaction. The proportion of actionable/druggable mutations was 38.9% (81/208), which was not significantly different between the cancer panel version 1.0 and version 2.0 (P = 0.476). Expert panel could discuss the findings and make sufficient reports.We confirmed the feasibility of NGS-based amplicon sequencing using biopsy samples, making the basis for nationwide genome screening for cancer patients using biopsy samples. Our results suggest that focused panel may be sufficient to detect major mutations.

SUBMITTER: Naito Y

PROVIDER: S-EPMC5974784 | biostudies-other | 2018 Jun

REPOSITORIES: biostudies-other

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Feasibility study of cancer genome alterations identified by next generation sequencing: ABC study.

Naito Yoichi Y Takahashi Hideaki H Shitara Kohei K Okamoto Wataru W Bando Hideaki H Kuwata Takeshi T Kuboki Yasutoshi Y Matsumoto Shingo S Miki Izumi I Yamanaka Takeharu T Watanabe Atsushi A Kojima Motohiro M

Japanese journal of clinical oncology 20180601 6

<h4>Background</h4>To confirm the feasibility and explore the clinical applicability of amplicon sequencing by next generation sequencing (NGS) of biopsy samples from patients with advanced solid tumors, we conducted a prospective study.<h4>Methods</h4>Patients with unresectable, advanced, or recurrent solid tumors were included. Key eligibility criteria were as follows: 20 years or older, any planned systemic therapy, adequate lesion for biopsy, and written informed consent. Samples were fixed ...[more]

PMID: 29659903

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Project description:Gastric cancer (GC) remains the second tumor caused death threat worldwide, and personalized medicine for GC is far from expectation. Finding novel, recurrently mutated genes through next-generation sequencing (NGS) is a powerful and productive approach. However, previous genomic data for GC are based on surgical resected samples while a large proportion of advanced gastric cancer (AGC) patients have already missed the chance for operation. The aim of this study is to assess frequent genomic alteration in AGC via biopsy samples. Here we performed targeted genomic sequencing of 78 AGC patients' tumor biopsies along with matched lymphocyte samples based on a 118 cancer related gene panel. In total, we observed 301 somatic nonsynonymous genomic alterations in 92 different genes, as well as 37 copy number gain events among 15 different genes (fold change 2-12), and validated the fold changes of ERBB2 copy number gains with IHC and FISH test showed an accuracy of 81.8%. Previously reported driver genes for gastric cancer (TP53, KMT2D, KMT2B, EGFR, PIK3CA, GNAQ, and ARID1A), and several unreported mutations (TGFBR2, RNF213, NF1, NSD1, and LRP2) showed high non-silent mutation prevalence (7.7%-34.6%). When comparing intestinal-type gastric cancer (IGC) with diffuse-type gastric cancer (DGC), TP53 and GNAQ appear to be more frequently mutated in IGC (P=0.028 and P=0.023, respectively), whereas LRP2, BRCA2 and FGFR3 mutations are not observed in IGC, but have 12.8%, 7.7% and 7.7% mutation rates, respectively, in DGC patients. Patients with one or more mutations in adherens junction pathway (CREBBP, EP300, CDH1, CTNNB1, EGFR, MET, TGFBR2 and ERBB2) or TGF-? signaling pathway (CREBBP, EP300, MYST4, KRAS and TGFBR2) showed significantly better overall survival (P=0.007 and P=0.014, respectively), consistent with The Cancer Genome Atlas (TCGA) cohort data. Importantly, 57 (73.1%) patients harbored at least one genomic alteration with potential treatments, making NGS-based drug target screening a viable option for AGC patients. Our study established a comprehensive genomic portrait of AGC, and identified several mutation signatures highly associated with clinical features, survival outcomes, which may be used to design future personalized treatments.

Dataset Information

Feasibility study of cancer genome alterations identified by next generation sequencing: ABC study.

Publications

Feasibility study of cancer genome alterations identified by next generation sequencing: ABC study.

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