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. 2018 Jun 1;48(6):559-564.
doi: 10.1093/jjco/hyy052.

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

Yoichi Naito  1 , Hideaki Takahashi  1 , Kohei Shitara  1 , Wataru Okamoto  1 , Hideaki Bando  1 , Takeshi Kuwata  1 , Yasutoshi Kuboki  1 , Shingo Matsumoto  1 , Izumi Miki  1 , Takeharu Yamanaka  2 , Atsushi Watanabe  3 , Motohiro Kojima  1
Affiliations

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

Yoichi Naito et al. Jpn J Clin Oncol. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Figures

Figure 1.
Figure 1.
CONSORT of patients and samples. A total of 232 patients were enrolled, and in 208 patients (89.7%) sequencing was successfully performed.
Figure 2.
Figure 2.
Frequency of nonsynonymous/nonsense mutations and indels in the entire cohort. TP53 mutations (41.8%) were the most frequently observed protein-altered mutations, followed by KRAS (16.3%), STK11 (12.5%), PIK3CA (12.0%), KIT (12.0%), MLH1 (7.2%), APC (5.8%), CTNNB1 (5.8%), MET (5.8%) and BRAF (4.8%) mutations.
Figure 3.
Figure 3.
Details of each case and mutation. The proportion of actionable/druggable mutations was 38.9% and detected across the tumor types.
See this image and copyright information in PMC

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