Somatic mutations in plasma cell-free DNA are diagnostic markers for esophageal squamous cell carcinoma recurrence

Masami Ueda, Tomohiro Iguchi, Takaaki Masuda, Yujiro Nakahara, Hidenari Hirata, Ryutaro Uchi, Atsushi Niida, Kota Momose, Shotaro Sakimura, Kenichi Chiba, Hidetoshi Eguchi, Shuhei Ito, Keishi Sugimachi, Makoto Yamasaki, Yutaka Suzuki, Satoru Miyano, Yuichiro Doki, Masaki Mori, Koshi Mimori

研究成果: ジャーナルへの寄稿記事

17 引用 (Scopus)

抄録

Objectives: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies owing to the high frequency of tumor recurrence. The identification of markers for early ESCC diagnosis and prediction of recurrence is expected to improve the long-term prognosis. Therefore, we searched for associations between tumor recurrence and cell-free DNA (cfDNA) mutations in blood plasma, which contains genetic markers for various cancer types. Experimental Design: Genomic DNA from tumors and cfDNA from plasma were obtained from 13 patients undergoing treatment for newly diagnosed ESCC. Nextgeneration sequencing of cfDNA in plasma was performed to identify mutations in 53 cancer-related genes, in which recurrent mutations were previously detected in ESCC. cfDNA mutational profiles were compared before and after tumor resection in four patients. Furthermore, somatic mutations in serial plasma samples were monitored after treatment in four patients. Results: We identified multiple concordant somatic mutations in cfDNA and primary tumor samples from 10 patients (83.3%) and in cfDNA and metastatic tumor samples from one patient (100%). Furthermore, the allele frequency of the concordant mutations in cfDNA changed concomitantly with tumor burden and increased approximately 6 months earlier than the detection of tumor recurrences by imaging tests in two patients. Conventional biomarkers, such as SCC and p53-Ab, did not reflect tumor recurrences. Conclusions: The present multigene panel, which enabled the diagnosis of tumor recurrence with greater accuracy than did using standard tumor markers or imaging methods, is expected to greatly facilitate standard, postoperative follow-up monitoring in ESCC.

元の言語英語
ページ(範囲)62280-62291
ページ数12
ジャーナルOncotarget
7
発行部数38
DOI
出版物ステータス出版済み - 1 1 2016

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Plasma Cells
Genetic Markers
Recurrence
Mutation
Neoplasms
DNA
Esophageal Squamous Cell Carcinoma
Neoplasm Genes
Tumor Biomarkers
Tumor Burden
Gene Frequency
Research Design
Biomarkers

All Science Journal Classification (ASJC) codes

  • Oncology

これを引用

Somatic mutations in plasma cell-free DNA are diagnostic markers for esophageal squamous cell carcinoma recurrence. / Ueda, Masami; Iguchi, Tomohiro; Masuda, Takaaki; Nakahara, Yujiro; Hirata, Hidenari; Uchi, Ryutaro; Niida, Atsushi; Momose, Kota; Sakimura, Shotaro; Chiba, Kenichi; Eguchi, Hidetoshi; Ito, Shuhei; Sugimachi, Keishi; Yamasaki, Makoto; Suzuki, Yutaka; Miyano, Satoru; Doki, Yuichiro; Mori, Masaki; Mimori, Koshi.

:: Oncotarget, 巻 7, 番号 38, 01.01.2016, p. 62280-62291.

研究成果: ジャーナルへの寄稿記事

Ueda, M, Iguchi, T, Masuda, T, Nakahara, Y, Hirata, H, Uchi, R, Niida, A, Momose, K, Sakimura, S, Chiba, K, Eguchi, H, Ito, S, Sugimachi, K, Yamasaki, M, Suzuki, Y, Miyano, S, Doki, Y, Mori, M & Mimori, K 2016, 'Somatic mutations in plasma cell-free DNA are diagnostic markers for esophageal squamous cell carcinoma recurrence', Oncotarget, 巻. 7, 番号 38, pp. 62280-62291. https://doi.org/10.18632/oncotarget.11409
Ueda, Masami ; Iguchi, Tomohiro ; Masuda, Takaaki ; Nakahara, Yujiro ; Hirata, Hidenari ; Uchi, Ryutaro ; Niida, Atsushi ; Momose, Kota ; Sakimura, Shotaro ; Chiba, Kenichi ; Eguchi, Hidetoshi ; Ito, Shuhei ; Sugimachi, Keishi ; Yamasaki, Makoto ; Suzuki, Yutaka ; Miyano, Satoru ; Doki, Yuichiro ; Mori, Masaki ; Mimori, Koshi. / Somatic mutations in plasma cell-free DNA are diagnostic markers for esophageal squamous cell carcinoma recurrence. :: Oncotarget. 2016 ; 巻 7, 番号 38. pp. 62280-62291.
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abstract = "Objectives: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies owing to the high frequency of tumor recurrence. The identification of markers for early ESCC diagnosis and prediction of recurrence is expected to improve the long-term prognosis. Therefore, we searched for associations between tumor recurrence and cell-free DNA (cfDNA) mutations in blood plasma, which contains genetic markers for various cancer types. Experimental Design: Genomic DNA from tumors and cfDNA from plasma were obtained from 13 patients undergoing treatment for newly diagnosed ESCC. Nextgeneration sequencing of cfDNA in plasma was performed to identify mutations in 53 cancer-related genes, in which recurrent mutations were previously detected in ESCC. cfDNA mutational profiles were compared before and after tumor resection in four patients. Furthermore, somatic mutations in serial plasma samples were monitored after treatment in four patients. Results: We identified multiple concordant somatic mutations in cfDNA and primary tumor samples from 10 patients (83.3{\%}) and in cfDNA and metastatic tumor samples from one patient (100{\%}). Furthermore, the allele frequency of the concordant mutations in cfDNA changed concomitantly with tumor burden and increased approximately 6 months earlier than the detection of tumor recurrences by imaging tests in two patients. Conventional biomarkers, such as SCC and p53-Ab, did not reflect tumor recurrences. Conclusions: The present multigene panel, which enabled the diagnosis of tumor recurrence with greater accuracy than did using standard tumor markers or imaging methods, is expected to greatly facilitate standard, postoperative follow-up monitoring in ESCC.",
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T1 - Somatic mutations in plasma cell-free DNA are diagnostic markers for esophageal squamous cell carcinoma recurrence

AU - Ueda, Masami

AU - Iguchi, Tomohiro

AU - Masuda, Takaaki

AU - Nakahara, Yujiro

AU - Hirata, Hidenari

AU - Uchi, Ryutaro

AU - Niida, Atsushi

AU - Momose, Kota

AU - Sakimura, Shotaro

AU - Chiba, Kenichi

AU - Eguchi, Hidetoshi

AU - Ito, Shuhei

AU - Sugimachi, Keishi

AU - Yamasaki, Makoto

AU - Suzuki, Yutaka

AU - Miyano, Satoru

AU - Doki, Yuichiro

AU - Mori, Masaki

AU - Mimori, Koshi

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Objectives: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies owing to the high frequency of tumor recurrence. The identification of markers for early ESCC diagnosis and prediction of recurrence is expected to improve the long-term prognosis. Therefore, we searched for associations between tumor recurrence and cell-free DNA (cfDNA) mutations in blood plasma, which contains genetic markers for various cancer types. Experimental Design: Genomic DNA from tumors and cfDNA from plasma were obtained from 13 patients undergoing treatment for newly diagnosed ESCC. Nextgeneration sequencing of cfDNA in plasma was performed to identify mutations in 53 cancer-related genes, in which recurrent mutations were previously detected in ESCC. cfDNA mutational profiles were compared before and after tumor resection in four patients. Furthermore, somatic mutations in serial plasma samples were monitored after treatment in four patients. Results: We identified multiple concordant somatic mutations in cfDNA and primary tumor samples from 10 patients (83.3%) and in cfDNA and metastatic tumor samples from one patient (100%). Furthermore, the allele frequency of the concordant mutations in cfDNA changed concomitantly with tumor burden and increased approximately 6 months earlier than the detection of tumor recurrences by imaging tests in two patients. Conventional biomarkers, such as SCC and p53-Ab, did not reflect tumor recurrences. Conclusions: The present multigene panel, which enabled the diagnosis of tumor recurrence with greater accuracy than did using standard tumor markers or imaging methods, is expected to greatly facilitate standard, postoperative follow-up monitoring in ESCC.

AB - Objectives: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies owing to the high frequency of tumor recurrence. The identification of markers for early ESCC diagnosis and prediction of recurrence is expected to improve the long-term prognosis. Therefore, we searched for associations between tumor recurrence and cell-free DNA (cfDNA) mutations in blood plasma, which contains genetic markers for various cancer types. Experimental Design: Genomic DNA from tumors and cfDNA from plasma were obtained from 13 patients undergoing treatment for newly diagnosed ESCC. Nextgeneration sequencing of cfDNA in plasma was performed to identify mutations in 53 cancer-related genes, in which recurrent mutations were previously detected in ESCC. cfDNA mutational profiles were compared before and after tumor resection in four patients. Furthermore, somatic mutations in serial plasma samples were monitored after treatment in four patients. Results: We identified multiple concordant somatic mutations in cfDNA and primary tumor samples from 10 patients (83.3%) and in cfDNA and metastatic tumor samples from one patient (100%). Furthermore, the allele frequency of the concordant mutations in cfDNA changed concomitantly with tumor burden and increased approximately 6 months earlier than the detection of tumor recurrences by imaging tests in two patients. Conventional biomarkers, such as SCC and p53-Ab, did not reflect tumor recurrences. Conclusions: The present multigene panel, which enabled the diagnosis of tumor recurrence with greater accuracy than did using standard tumor markers or imaging methods, is expected to greatly facilitate standard, postoperative follow-up monitoring in ESCC.

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JF - Oncotarget

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