nach oben

Erschienen in:

01.11.2013 | Original Article

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

verfasst von: Masato Kojima, Eiso Hiyama, Ikuko Fukuba, Emi Yamaoka, Yuka Ueda, Yoshiyuki Onitake, Shou Kurihara, Taijiro Sueda

Erschienen in: Pediatric Surgery International | Ausgabe 11/2013

Einloggen, um Zugang zu erhalten

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.

Ohtsu K, Hiyama E, Ichikawa T, Matsuura Y, Yokoyama T (1997) Clinical Investigation of neuroblastoma with partial deletion in the short arm of chromosome 1. Clin Cancer Res 3:1221–1228PubMed

Hiyama E, Hiyama K, Ohtsu K, Yamaoka H, Fukuba I, Matsuura Y, Yokoyama T (2001) Biological characteristics of neuroblastoma with partial deletion in the short arm of chromosome 1. Med Pediatr Oncol 36:67–74PubMedCrossRef

Plantaz D, Mohapatra G, Matthay KK, Pellarin M, Seeger RC, Feuerstein BG (1997) Gain of chromosome 17 is the most frequent abnormality detected in neuroblastoma by comparative genomic hybridization. Am J Pathol 150:81–89PubMed

Maris JM, Guo C, White PS, Hogarty MD, Thompson PM, Stram DO, Gerbing R, Matthay KK, Seeger RC, Brodeur GM (2001) Allelic deletion at chromosome bands 11q14-23 is common in neuroblastoma. Med Pediatr Oncol 36:24–27PubMedCrossRef

Hiyama E, Yokoyama T, Ichikawa T, Ishii T, Hiyama K (1990) N-myc gene amplification and other prognostic associated factors in neuroblastoma. J Pediatr Surg 25:1095–1099PubMedCrossRef

Ambros PF, Ambros IM, Brodeur GM, Haber M, Khan J, Nakagawara A, Schleiermacher G, Speleman F, Spitz R, London WB, Cohn SL, Pearson AD, Maris JM (2009) International consensus for neuroblastoma molecular diagnostics: report from the international neuroblastoma risk group (INRG) Biology Committee. Br J Cancer 100:1471–1482PubMedCrossRef

Kaneko M, Tsuchida Y, Uchino J, Takeda T, Iwafuchi M, Ohnuma N, Mugishima H, Yokoyama J, Nishihira H, Nakada K, Sasaki S, Sawada T, Kawa K, Nagahara N, Suita S, Sawaguchi S (1999) 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 21:190–197PubMedCrossRef

Hiyama E, Hiyama K, Yokoyama T (1991) Neuroblastoma with DNA amplification and rearrangement in the N-myc gene region. Cancer Res 51:1946–1951PubMed

Hiyama E, Hiyama K (2009) Diagnostic and prognostic molecular markers in neuroblastoma, 1st edn. Transworld Research Network, Kerala

10.

Gotoh T, Hosoi H, Iehara T, Kuwahara Y, Osone S, Tsuchiya K, Ohira M, Nakagawara A, Kuroda H, Sugimoto T (2005) Prediction of MYCN amplification in neuroblastoma using serum DNA and real-time quantitative polymerase chain reaction. J Clin Oncol 23:5205–5210PubMedCrossRef

11.

Hiyama E, Hiyama K (2005) Molecular and biological heterogeneity in neuroblastoma. Curr Genomics 6:319–332CrossRef

12.

Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342:705–708PubMedCrossRef

13.

Kopreski MS, Benko FA, Kwee C, Leitzel KE, Eskander E, Lipton A, Gocke CD (1997) Detection of mutant K-ras DNA in plasma or serum of patients with colorectal cancer. Br J Cancer 76:1293–1299PubMedCrossRef

14.

Chiang PW, Beer DG, Wei WL, Orringer MB, Kurnit DM (1999) Detection of erbB-2 amplifications in tumors and sera from esophageal carcinoma patients. Clin Cancer Res 5:1381–1386PubMed

15.

Combaret V, Audoynaud C, Iacono I, Favrot MC, Schell M, Bergeron C, Puisieux A (2002) Circulating MYCN DNA as a tumor-specific marker in neuroblastoma patients. Cancer Res 62:3646–3648PubMed

Titel: Detection of MYCN amplification using blood plasma: noninvasive therapy evaluation and prediction of prognosis in neuroblastoma
verfasst von: Masato Kojima
Eiso Hiyama
Ikuko Fukuba
Emi Yamaoka
Yuka Ueda
Yoshiyuki Onitake
Shou Kurihara
Taijiro Sueda
Publikationsdatum: 01.11.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Surgery International / Ausgabe 11/2013
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-013-3374-9

Neu im Fachgebiet Pädiatrie

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

17.05.2024 Klinik aktuell Nachrichten

Sie sei „ethisch geboten“, meint Gesundheitsminister Karl Lauterbach: mehr Transparenz über die Qualität von Klinikbehandlungen. Um sie abzubilden, lässt er gegen den Widerstand vieler Länder einen virtuellen Klinik-Atlas freischalten.

ADHS-Medikation erhöht das kardiovaskuläre Risiko

16.05.2024 Herzinsuffizienz Nachrichten

Erwachsene, die Medikamente gegen das Aufmerksamkeitsdefizit-Hyperaktivitätssyndrom einnehmen, laufen offenbar erhöhte Gefahr, an Herzschwäche zu erkranken oder einen Schlaganfall zu erleiden. Es scheint eine Dosis-Wirkungs-Beziehung zu bestehen.

Erstmanifestation eines Diabetes-Typ-1 bei Kindern: Ein Notfall!

16.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Manifestiert sich ein Typ-1-Diabetes bei Kindern, ist das ein Notfall – ebenso wie eine diabetische Ketoazidose. Die Grundsäulen der Therapie bestehen aus Rehydratation, Insulin und Kaliumgabe. Insulin ist das Medikament der Wahl zur Behandlung der Ketoazidose.

Frühe Hypertonie erhöht späteres kardiovaskuläres Risiko

16.05.2024 Arterielle Hypertonie in der Pädiatrie Nachrichten

Wie wichtig es ist, pädiatrische Patienten auf Bluthochdruck zu screenen, zeigt eine kanadische Studie: Hypertone Druckwerte in Kindheit und Jugend steigern das Risiko für spätere kardiovaskuläre Komplikationen.

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

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