KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.

The promising results of anaplastic lymphoma kinase (ALK) inhibitors have changed the significance of ALK fusions in several types of cancer. These fusions are no longer mere research targets or diagnostic markers, but they are now directly linked to the therapeutic benefit of patients. However, mos...

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Autores principales:	Yuki Togashi, Manabu Soda, Seiji Sakata, Emiko Sugawara, Satoko Hatano, Reimi Asaka, Takashi Nakajima, Hiroyuki Mano, Kengo Takeuchi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3cd968b320cf479fb7e56c68f8941206
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spelling	oai:doaj.org-article:3cd968b320cf479fb7e56c68f89412062021-11-18T07:28:38ZKLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.1932-620310.1371/journal.pone.0031323https://doaj.org/article/3cd968b320cf479fb7e56c68f89412062012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22347464/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The promising results of anaplastic lymphoma kinase (ALK) inhibitors have changed the significance of ALK fusions in several types of cancer. These fusions are no longer mere research targets or diagnostic markers, but they are now directly linked to the therapeutic benefit of patients. However, most available tumor tissues in clinical settings are formalin-fixed and paraffin-embedded (FFPE), and this significantly limits detailed genetic studies in many clinical cases. Although recent technical improvements have allowed the analysis of some known mutations in FFPE tissues, identifying unknown fusion genes by using only FFPE tissues remains difficult. We developed a 5'-rapid amplification of cDNA ends-based system optimized for FFPE tissues and evaluated this system on a lung cancer tissue with ALK rearrangement and without the 2 known ALK fusions EML4-ALK and KIF5B-ALK. With this system, we successfully identified a novel ALK fusion, KLC1-ALK. The result was confirmed by reverse transcription-polymerase chain reaction and fluorescence in situ hybridization. Then, we synthesized the putative full-length cDNA of KLC1-ALK and demonstrated the transforming potential of the fusion kinase with assays using mouse 3T3 cells. To the best of our knowledge, KLC1-ALK is the first novel oncogenic fusion identified using only FFPE tissues. This finding will broaden the potential value of archival FFPE tissues and provide further biological and clinical insights into ALK-positive lung cancer.Yuki TogashiManabu SodaSeiji SakataEmiko SugawaraSatoko HatanoReimi AsakaTakashi NakajimaHiroyuki ManoKengo TakeuchiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31323 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuki Togashi Manabu Soda Seiji Sakata Emiko Sugawara Satoko Hatano Reimi Asaka Takashi Nakajima Hiroyuki Mano Kengo Takeuchi KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.
description	The promising results of anaplastic lymphoma kinase (ALK) inhibitors have changed the significance of ALK fusions in several types of cancer. These fusions are no longer mere research targets or diagnostic markers, but they are now directly linked to the therapeutic benefit of patients. However, most available tumor tissues in clinical settings are formalin-fixed and paraffin-embedded (FFPE), and this significantly limits detailed genetic studies in many clinical cases. Although recent technical improvements have allowed the analysis of some known mutations in FFPE tissues, identifying unknown fusion genes by using only FFPE tissues remains difficult. We developed a 5'-rapid amplification of cDNA ends-based system optimized for FFPE tissues and evaluated this system on a lung cancer tissue with ALK rearrangement and without the 2 known ALK fusions EML4-ALK and KIF5B-ALK. With this system, we successfully identified a novel ALK fusion, KLC1-ALK. The result was confirmed by reverse transcription-polymerase chain reaction and fluorescence in situ hybridization. Then, we synthesized the putative full-length cDNA of KLC1-ALK and demonstrated the transforming potential of the fusion kinase with assays using mouse 3T3 cells. To the best of our knowledge, KLC1-ALK is the first novel oncogenic fusion identified using only FFPE tissues. This finding will broaden the potential value of archival FFPE tissues and provide further biological and clinical insights into ALK-positive lung cancer.
format	article
author	Yuki Togashi Manabu Soda Seiji Sakata Emiko Sugawara Satoko Hatano Reimi Asaka Takashi Nakajima Hiroyuki Mano Kengo Takeuchi
author_facet	Yuki Togashi Manabu Soda Seiji Sakata Emiko Sugawara Satoko Hatano Reimi Asaka Takashi Nakajima Hiroyuki Mano Kengo Takeuchi
author_sort	Yuki Togashi
title	KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.
title_short	KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.
title_full	KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.
title_fullStr	KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.
title_full_unstemmed	KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.
title_sort	klc1-alk: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3cd968b320cf479fb7e56c68f8941206
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KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.

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