Oncotarget

Research Papers:

Mutational analysis of multiple lung cancers: Discrimination between primary and metastatic lung cancers by genomic profile

Taichiro Goto _, Yosuke Hirotsu, Hitoshi Mochizuki, Takahiro Nakagomi, Daichi Shikata, Yujiro Yokoyama, Toshio Oyama, Kenji Amemiya, Kenichiro Okimoto and Masao Omata

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Oncotarget. 2017; 8:31133-31143. https://doi.org/10.18632/oncotarget.16096

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Abstract

Taichiro Goto1,*, Yosuke Hirotsu2,*, Hitoshi Mochizuki2, Takahiro Nakagomi1, Daichi Shikata1, Yujiro Yokoyama1, Toshio Oyama3, Kenji Amemiya2, Kenichiro Okimoto2, Masao Omata2,4

1Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Yamanashi, Japan

2Genome Analysis Center, Yamanashi Central Hospital, Yamanashi, Japan

3Department of Pathology, Yamanashi Central Hospital, Yamanashi, Japan

4University of Tokyo, Tokyo, Japan

*These authors contributed equally to this work

Correspondence to:

Taichiro Goto, email: taichiro@1997.jukuin.keio.ac.jp

Keywords: lung cancer, multiple cancers, metastasis, mutation, next-generation sequencing

Received: November 30, 2016     Accepted: February 28, 2017     Published: March 10, 2017

ABSTRACT

In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed. In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic. In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.


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