NTRK fusion in Japanese colorectal adenocarcinomas
Abstract NTRK fusion-positive tumors are known to be highly sensitive to TRK inhibitors, such as larotrectinib and entrectinib. Therefore, identification of patients who can potentially benefit from these inhibitors is important; however, the frequency of NTRK fusions in Japanese patients with color...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-85075-y |
| _version_ | 1818435816469299200 |
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| author | Yuya Yamashiro Taisei Kurihara Takuo Hayashi Yoshiyuki Suehara Takashi Yao Shunsuke Kato Tsuyoshi Saito |
| author_facet | Yuya Yamashiro Taisei Kurihara Takuo Hayashi Yoshiyuki Suehara Takashi Yao Shunsuke Kato Tsuyoshi Saito |
| author_sort | Yuya Yamashiro |
| collection | DOAJ |
| description | Abstract NTRK fusion-positive tumors are known to be highly sensitive to TRK inhibitors, such as larotrectinib and entrectinib. Therefore, identification of patients who can potentially benefit from these inhibitors is important; however, the frequency of NTRK fusions in Japanese patients with colorectal cancer (CRC) is unknown. We performed pan-TRK staining using TMA-based immunohistochemistry (IHC) on samples from 971 consecutive Japanese CRC cases from a single institution. Positive cases were further analyzed using NanoString and subsequent targeted RNA sequencing. We found three positive cases using TRK-IHC. Furthermore, the Nanostring assay supported the presence of NTRK fusion in these cases. Subsequent targeted RNA-sequencing and RT-PCR revealed two cases with TPM3-NTRK1 and one with TPR-NTRK1. The TNM stages of these cases were stage I, stage IIA, and stage IIIB, and two showed microsatellite instability-high status. Next-generation sequencing analysis using Cancer hotspot panel revealed TP53 and SMAD4 mutations in separate cases. IHC of β-catenin did not show nuclear accumulation. We found three cases (0.31%) of CRC with NTRK1 fusion among 971 consecutive Japanese CRC cases. No potential driver alterations other than NTRK fusion were identified in these three patients. |
| first_indexed | 2024-12-14T16:58:54Z |
| format | Article |
| id | doaj.art-d4b40b23678a4b69aaac2112c31e7373 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T16:58:54Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d4b40b23678a4b69aaac2112c31e73732022-12-21T22:53:54ZengNature PortfolioScientific Reports2045-23222021-03-011111910.1038/s41598-021-85075-yNTRK fusion in Japanese colorectal adenocarcinomasYuya Yamashiro0Taisei Kurihara1Takuo Hayashi2Yoshiyuki Suehara3Takashi Yao4Shunsuke Kato5Tsuyoshi Saito6Department of Human Pathology, Juntendo University School of MedicineDepartment of Human Pathology, Juntendo University School of MedicineDepartment of Human Pathology, Juntendo University School of MedicineDepartment of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of MedicineDepartment of Human Pathology, Juntendo University School of MedicineDepartment of Medical Oncology, Juntendo University School of MedicineDepartment of Human Pathology, Juntendo University School of MedicineAbstract NTRK fusion-positive tumors are known to be highly sensitive to TRK inhibitors, such as larotrectinib and entrectinib. Therefore, identification of patients who can potentially benefit from these inhibitors is important; however, the frequency of NTRK fusions in Japanese patients with colorectal cancer (CRC) is unknown. We performed pan-TRK staining using TMA-based immunohistochemistry (IHC) on samples from 971 consecutive Japanese CRC cases from a single institution. Positive cases were further analyzed using NanoString and subsequent targeted RNA sequencing. We found three positive cases using TRK-IHC. Furthermore, the Nanostring assay supported the presence of NTRK fusion in these cases. Subsequent targeted RNA-sequencing and RT-PCR revealed two cases with TPM3-NTRK1 and one with TPR-NTRK1. The TNM stages of these cases were stage I, stage IIA, and stage IIIB, and two showed microsatellite instability-high status. Next-generation sequencing analysis using Cancer hotspot panel revealed TP53 and SMAD4 mutations in separate cases. IHC of β-catenin did not show nuclear accumulation. We found three cases (0.31%) of CRC with NTRK1 fusion among 971 consecutive Japanese CRC cases. No potential driver alterations other than NTRK fusion were identified in these three patients.https://doi.org/10.1038/s41598-021-85075-y |
| spellingShingle | Yuya Yamashiro Taisei Kurihara Takuo Hayashi Yoshiyuki Suehara Takashi Yao Shunsuke Kato Tsuyoshi Saito NTRK fusion in Japanese colorectal adenocarcinomas Scientific Reports |
| title | NTRK fusion in Japanese colorectal adenocarcinomas |
| title_full | NTRK fusion in Japanese colorectal adenocarcinomas |
| title_fullStr | NTRK fusion in Japanese colorectal adenocarcinomas |
| title_full_unstemmed | NTRK fusion in Japanese colorectal adenocarcinomas |
| title_short | NTRK fusion in Japanese colorectal adenocarcinomas |
| title_sort | ntrk fusion in japanese colorectal adenocarcinomas |
| url | https://doi.org/10.1038/s41598-021-85075-y |
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