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Detection of MYCN amplification using blood plasma: noninvasive therapy evaluation and prediction of prognosis in neuroblastoma

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Abstract

Purpose

Amplification of neuroblastoma derived (avian) v-myc myelocytomatosis viral related oncogene (MYCN) is an important risk-stratified indicator in neuroblastoma. To evaluate the feasibility of noninvasive measurement of MYCN amplification, we analyzed MYCN amplification in stored blood plasma samples.

Methods

We used quantitative real-time PCR to determine MYCN copy numbers in plasma-derived DNA of 10 healthy volunteers and 50 neuroblastoma cases. The copy number was calculated as the ratio of copies of MYCN to those of a reference gene. Plasma samples obtained after surgery or neoadjuvant therapy were also analyzed in five cases and four cases, respectively.

Results

In 34 neuroblastoma cases, MYCN was non-amplified in both tumor tissue and blood plasma. In 16 neuroblastoma cases, MYCN was amplified in both tumor tissue and blood plasma; 13 of the 16 cases showed poor outcomes. MYCN amplification was undetectable in blood plasma shortly after surgery or neoadjuvant therapy. The correlation coefficient between MYCN copy numbers in tumor tissue and in blood plasma was approximately 0.9.

Conclusion

We can detect MYCN amplification of tumor tissue noninvasively and quantitatively by measuring the MYCN copy number in blood plasma. Determination of MYCN copy number in plasma may be useful when evaluating surgery and neoadjuvant chemotherapy.

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Acknowledgments

Supported by Grant-in-Aid for Scientific Research (A) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Masato Kojima, Eiso Hiyama, Yuka Ueda, Yoshiyuki Onitake, Shou Kurihara & Taijiro Sueda

  2. Natural Science Center for Basic Research and Development, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Eiso Hiyama, Ikuko Fukuba & Emi Yamaoka

Authors
  1. Masato Kojima
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  2. Eiso Hiyama
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  3. Ikuko Fukuba
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  4. Emi Yamaoka
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  5. Yuka Ueda
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  6. Yoshiyuki Onitake
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  7. Shou Kurihara
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  8. Taijiro Sueda
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Correspondence to Eiso Hiyama.

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Kojima, M., Hiyama, E., Fukuba, I. et al. Detection of MYCN amplification using blood plasma: noninvasive therapy evaluation and prediction of prognosis in neuroblastoma. Pediatr Surg Int 29, 1139–1145 (2013). https://doi.org/10.1007/s00383-013-3374-9

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  • DOI: https://doi.org/10.1007/s00383-013-3374-9

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