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. 2017 Jul;108(7):1440-1446.
doi: 10.1111/cas.13265. Epub 2017 May 22.

Clinical sequencing using a next-generation sequencing-based multiplex gene assay in patients with advanced solid tumors

Tadayuki Kou  1 , Masashi Kanai  1 , Yoshihiro Yamamoto  1 , Mayumi Kamada  2 , Masahiko Nakatsui  2 , Tomohiro Sakuma  3 , Hiroaki Mochizuki  3 , Akinori Hiroshima  3 , Aiko Sugiyama  4 , Eijiro Nakamura  4 , Hidehiko Miyake  5 , Sachiko Minamiguchi  6 , Kyoichi Takaori  7 , Shigemi Matsumoto  1 , Hironori Haga  6 , Hiroshi Seno  8 , Shinji Kosugi  9 , Yasushi Okuno  2 , Manabu Muto  1
Affiliations

Clinical sequencing using a next-generation sequencing-based multiplex gene assay in patients with advanced solid tumors

Tadayuki Kou et al. Cancer Sci. 2017 Jul.

Abstract

Advances in next-generation sequencing (NGS) technologies have enabled physicians to test for genomic alterations in multiple cancer-related genes at once in daily clinical practice. In April 2015, we introduced clinical sequencing using an NGS-based multiplex gene assay (OncoPrime) certified by the Clinical Laboratory Improvement Amendment. This assay covers the entire coding regions of 215 genes and the rearrangement of 17 frequently rearranged genes with clinical relevance in human cancers. The principal indications for the assay were cancers of unknown primary site, rare tumors, and any solid tumors that were refractory to standard chemotherapy. A total of 85 patients underwent testing with multiplex gene assay between April 2015 and July 2016. The most common solid tumor types tested were pancreatic (n = 19; 22.4%), followed by biliary tract (n = 14; 16.5%), and tumors of unknown primary site (n = 13; 15.3%). Samples from 80 patients (94.1%) were successfully sequenced. The median turnaround time was 40 days (range, 18-70 days). Potentially actionable mutations were identified in 69 of 80 patients (86.3%) and were most commonly found in TP53 (46.3%), KRAS (23.8%), APC (18.8%), STK11 (7.5%), and ATR (7.5%). Nine patients (13.0%) received a subsequent therapy based on the NGS assay results. Implementation of clinical sequencing using an NGS-based multiplex gene assay was feasible in the clinical setting and identified potentially actionable mutations in more than 80% of patients. Current challenges are to incorporate this genomic information into better therapeutic decision making.

Keywords: Actionable mutation; genotype-directed therapy; multiplex gene assay; next-generation sequencing; precision cancer medicine.

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Figures

Figure 1
Figure 1
Feasibility of the next‐generation sequencing (NGS)‐based multiplex gene assay. NGS success means that NGS was successfully completed, and the treating physician could receive the NGS assay results from the laboratory. Also, NGS failure means that NGS was not successfully completed, and the treating physician could not receive the NGS assay results.
Figure 2
Figure 2
Heat map describing potentially actionable mutations identified in each patient. Each column represents one patient, and each row represents one gene. Potentially actionable mutations are shown in blue.
Figure 3
Figure 3
Distribution of patients according to the availability of drugs suggested by next‐generation sequencing (NGS) assay results.
See this image and copyright information in PMC

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