Detection of MYCN Amplification Using Blood Plasma: Noninvasive Therapy Evaluation and Prediction of Prognosis in Neuroblastoma

Overview

Journal Pediatr Surg Int

Specialties General Surgery
Pediatrics

Date 2013 Sep 12

PMID 24022278

Citations 18

Authors

Masato Kojima

Eiso Hiyama

Ikuko Fukuba

Emi Yamaoka

Yuka Ueda

Yoshiyuki Onitake

Shou Kurihara

Taijiro Sueda

Affiliations

Soon will be listed here.

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 nonamplified 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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References

Gotoh T, Hosoi H, Iehara T, Kuwahara Y, Osone S, Tsuchiya K . Prediction of MYCN amplification in neuroblastoma using serum DNA and real-time quantitative polymerase chain reaction. J Clin Oncol. 2005; 23(22):5205-10. DOI: 10.1200/JCO.2005.02.014. View

Hiyama E, Yokoyama T, Ichikawa T, Ishii T, Hiyama K . N-myc gene amplification and other prognosis-associated factors in neuroblastoma. J Pediatr Surg. 1990; 25(10):1095-9. DOI: 10.1016/0022-3468(90)90227-z. View

Plantaz D, Mohapatra G, Matthay K, Pellarin M, Seeger R, Feuerstein B . Gain of chromosome 17 is the most frequent abnormality detected in neuroblastoma by comparative genomic hybridization. Am J Pathol. 1997; 150(1):81-9. PMC: 1858505. View

Ambros P, Ambros I, Brodeur G, Haber M, Khan J, Nakagawara A . International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br J Cancer. 2009; 100(9):1471-82. PMC: 2694415. DOI: 10.1038/sj.bjc.6605014. View

Ohtsu K, Hiyama E, Ichikawa T, Matsuura Y, Yokoyama T . Clinical investigation of neuroblastoma with partial deletion in the short arm of chromosome 1. Clin Cancer Res. 1997; 3(7):1221-8. View

Hiyama E, Hiyama K, Yokoyama T . Neuroblastoma with DNA amplification and rearrangement in the N-myc gene region. Cancer Res. 1991; 51(7):1946-51. View

Kopreski M, Benko F, Kwee C, Leitzel K, Eskander E, Lipton A . Detection of mutant K-ras DNA in plasma or serum of patients with colorectal cancer. Br J Cancer. 1997; 76(10):1293-9. PMC: 2228153. DOI: 10.1038/bjc.1997.551. View

Hiyama E, Hiyama K, Ohtsu K, Yamaoka H, Fukuba I, Matsuura Y . Biological characteristics of neuroblastoma with partial deletion in the short arm of chromosome 1. Med Pediatr Oncol. 2001; 36(1):67-74. DOI: 10.1002/1096-911X(20010101)36:1<67::AID-MPO1017>3.0.CO;2-S. View

Combaret V, Audoynaud C, Iacono I, Favrot M, Schell M, Bergeron C . Circulating MYCN DNA as a tumor-specific marker in neuroblastoma patients. Cancer Res. 2002; 62(13):3646-8. View

10.

Maris J, Guo C, White P, Hogarty M, Thompson P, Stram D . Allelic deletion at chromosome bands 11q14-23 is common in neuroblastoma. Med Pediatr Oncol. 2001; 36(1):24-7. DOI: 10.1002/1096-911X(20010101)36:1<24::AID-MPO1007>3.0.CO;2-7. View

11.

Nigro J, Baker S, Preisinger A, Jessup J, Hostetter R, Cleary K . Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989; 342(6250):705-8. DOI: 10.1038/342705a0. View

12.

Chiang P, Beer D, Wei W, Orringer M, Kurnit D . Detection of erbB-2 amplifications in tumors and sera from esophageal carcinoma patients. Clin Cancer Res. 1999; 5(6):1381-6. View

13.

Kaneko M, Tsuchida Y, Uchino J, Takeda T, IWAFUCHI M, Ohnuma N . Treatment results of advanced neuroblastoma with the first Japanese study group protocol. Study Group of Japan for Treatment of Advanced Neuroblastoma. J Pediatr Hematol Oncol. 1999; 21(3):190-7. DOI: 10.1097/00043426-199905000-00006. View