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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yuya Yamashiro, Taisei Kurihara, Takuo Hayashi, Yoshiyuki Suehara, Takashi Yao, Shunsuke Kato, Tsuyoshi Saito
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d4b40b23678a4b69aaac2112c31e7373
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d4b40b23678a4b69aaac2112c31e7373
record_format	dspace
spelling	oai:doaj.org-article:d4b40b23678a4b69aaac2112c31e73732021-12-02T13:34:32ZNTRK fusion in Japanese colorectal adenocarcinomas10.1038/s41598-021-85075-y2045-2322https://doaj.org/article/d4b40b23678a4b69aaac2112c31e73732021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85075-yhttps://doaj.org/toc/2045-2322Abstract 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.Yuya YamashiroTaisei KuriharaTakuo HayashiYoshiyuki SueharaTakashi YaoShunsuke KatoTsuyoshi SaitoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuya Yamashiro Taisei Kurihara Takuo Hayashi Yoshiyuki Suehara Takashi Yao Shunsuke Kato Tsuyoshi Saito NTRK fusion in Japanese colorectal adenocarcinomas
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.
format	article
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
title	NTRK fusion in Japanese colorectal adenocarcinomas
title_short	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_sort	ntrk fusion in japanese colorectal adenocarcinomas
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d4b40b23678a4b69aaac2112c31e7373
work_keys_str_mv	AT yuyayamashiro ntrkfusioninjapanesecolorectaladenocarcinomas AT taiseikurihara ntrkfusioninjapanesecolorectaladenocarcinomas AT takuohayashi ntrkfusioninjapanesecolorectaladenocarcinomas AT yoshiyukisuehara ntrkfusioninjapanesecolorectaladenocarcinomas AT takashiyao ntrkfusioninjapanesecolorectaladenocarcinomas AT shunsukekato ntrkfusioninjapanesecolorectaladenocarcinomas AT tsuyoshisaito ntrkfusioninjapanesecolorectaladenocarcinomas
_version_	1718392823943790592

NTRK fusion in Japanese colorectal adenocarcinomas

Ejemplares similares