Detection of MYCN amplification using blood plasma: noninvasive therapy evaluation and prediction of prognosis in neuroblastoma
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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.
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.
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.
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.
KeywordsNeuroblastoma MYCN Amplification Real-time PCR Plasma
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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