HER2 genomic amplification in circulating tumor DNA from patients with cetuximab-resistant colorectal cancer

Naoki Takegawa, Kimio Yonesaka, Kazuko Sakai, Hiroto Ueda, Satomi Watanabe, Yoshikane Nonagase, Tatsuya Okuno, Masayuki Takeda, Osamu Maenishi, Junji Tsurutani, Taroh Satoh, Isamu Okamoto, Kazuto Nishio, Takao Tamura, Kazuhiko Nakagawa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS benefit from epidermal growth factor receptor (EGFR)-targeted therapy. However, patients who are treated with anti-EGFR antibodies will eventually develop the resistance to those agents. HER2 amplification is one of the mechanisms conferring resistance to anti-EGFR antibody therapy and could therefore be a potential therapeutic target. The aim of this study was to detect HER2 amplification in circulating tumor DNA (ctDNA) from patients with CRC and acquired resistance to anti-EGFR antibody therapy Results: Our data showed that 22% (4/18) of patients in the cohort exhibited HER2 amplification. One of these patients was found to be positive for HER2 amplification in matched tumor specimens collected after cetuximab therapy, at which point the patient had acquired cetuximab resistance, despite being negative for HER2 amplification prior to therapy. Methods: We analyzed plasma ctDNA using digital polymerase chain reaction (PCR) from 18 patients with CRC, who had been treated with anti-EGFR antibody-based therapy (cetuximab) and subsequently acquired resistant cetuximab. HER2 gene copy number was analyzed using fluorescence in situ hybridization in tumor samples before and after acquisition of resistance to cetuximab-based therapy. Conclusion: Analysis of plasma ctDNA by digital PCR could be useful for detecting HER2 amplification in patients with CRC who were resistant to anti-EGFR antibody therapy.

Original languageEnglish
Pages (from-to)3453-3460
Number of pages8
JournalOncotarget
Volume7
Issue number3
DOIs
Publication statusPublished - Jan 1 2016

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Colorectal Neoplasms
Epidermal Growth Factor Receptor
DNA
Neoplasms
Antibodies
Therapeutics
erbB-2 Genes
Cetuximab
Polymerase Chain Reaction
Gene Dosage
DNA-Directed DNA Polymerase
Fluorescence In Situ Hybridization

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Takegawa, N., Yonesaka, K., Sakai, K., Ueda, H., Watanabe, S., Nonagase, Y., ... Nakagawa, K. (2016). HER2 genomic amplification in circulating tumor DNA from patients with cetuximab-resistant colorectal cancer. Oncotarget, 7(3), 3453-3460. https://doi.org/10.18632/oncotarget.6498

HER2 genomic amplification in circulating tumor DNA from patients with cetuximab-resistant colorectal cancer. / Takegawa, Naoki; Yonesaka, Kimio; Sakai, Kazuko; Ueda, Hiroto; Watanabe, Satomi; Nonagase, Yoshikane; Okuno, Tatsuya; Takeda, Masayuki; Maenishi, Osamu; Tsurutani, Junji; Satoh, Taroh; Okamoto, Isamu; Nishio, Kazuto; Tamura, Takao; Nakagawa, Kazuhiko.

In: Oncotarget, Vol. 7, No. 3, 01.01.2016, p. 3453-3460.

Research output: Contribution to journalArticle

Takegawa, N, Yonesaka, K, Sakai, K, Ueda, H, Watanabe, S, Nonagase, Y, Okuno, T, Takeda, M, Maenishi, O, Tsurutani, J, Satoh, T, Okamoto, I, Nishio, K, Tamura, T & Nakagawa, K 2016, 'HER2 genomic amplification in circulating tumor DNA from patients with cetuximab-resistant colorectal cancer', Oncotarget, vol. 7, no. 3, pp. 3453-3460. https://doi.org/10.18632/oncotarget.6498
Takegawa, Naoki ; Yonesaka, Kimio ; Sakai, Kazuko ; Ueda, Hiroto ; Watanabe, Satomi ; Nonagase, Yoshikane ; Okuno, Tatsuya ; Takeda, Masayuki ; Maenishi, Osamu ; Tsurutani, Junji ; Satoh, Taroh ; Okamoto, Isamu ; Nishio, Kazuto ; Tamura, Takao ; Nakagawa, Kazuhiko. / HER2 genomic amplification in circulating tumor DNA from patients with cetuximab-resistant colorectal cancer. In: Oncotarget. 2016 ; Vol. 7, No. 3. pp. 3453-3460.
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AU - Watanabe, Satomi

AU - Nonagase, Yoshikane

AU - Okuno, Tatsuya

AU - Takeda, Masayuki

AU - Maenishi, Osamu

AU - Tsurutani, Junji

AU - Satoh, Taroh

AU - Okamoto, Isamu

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AU - Tamura, Takao

AU - Nakagawa, Kazuhiko

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N2 - Background: Patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS benefit from epidermal growth factor receptor (EGFR)-targeted therapy. However, patients who are treated with anti-EGFR antibodies will eventually develop the resistance to those agents. HER2 amplification is one of the mechanisms conferring resistance to anti-EGFR antibody therapy and could therefore be a potential therapeutic target. The aim of this study was to detect HER2 amplification in circulating tumor DNA (ctDNA) from patients with CRC and acquired resistance to anti-EGFR antibody therapy Results: Our data showed that 22% (4/18) of patients in the cohort exhibited HER2 amplification. One of these patients was found to be positive for HER2 amplification in matched tumor specimens collected after cetuximab therapy, at which point the patient had acquired cetuximab resistance, despite being negative for HER2 amplification prior to therapy. Methods: We analyzed plasma ctDNA using digital polymerase chain reaction (PCR) from 18 patients with CRC, who had been treated with anti-EGFR antibody-based therapy (cetuximab) and subsequently acquired resistant cetuximab. HER2 gene copy number was analyzed using fluorescence in situ hybridization in tumor samples before and after acquisition of resistance to cetuximab-based therapy. Conclusion: Analysis of plasma ctDNA by digital PCR could be useful for detecting HER2 amplification in patients with CRC who were resistant to anti-EGFR antibody therapy.

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