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

Abstract

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.

Shallow Whole Genome Sequencing on Circulating Cell-Free DNA Allows Reliable Noninvasive Copy-Number Profiling in Neuroblastoma Patients

“…Determination of MYCN amplification status is important because it is a biomarker strongly associated with unfavorable outcome of NB disease (31,32). MYCN amplification detection has already been described in cfDNA, but most of these studies relied on real-time quantitative PCR or digital droplet PCR (18,(45)(46)(47). Our sWGS platform allowed the identification of MYCN amplification in all 13 cases with described MYCN amplification in the tumor cells.…”

Advances in the translational genomics of neuroblastoma: From improving risk stratification and revealing novel biology to identifying actionable genomic alterations

“…Methods for detecting ctDNA have evolved, and techniques now exist that can detect rare ctDNA variants in a complex mixture of DNA with high sensitivity, and these techniques have the ability to detect the tumor‐derived DNA variants (ie, point mutations) that make up ≤ 0.01% of the total cell‐free DNA in the plasma . It has been observed that children with neuroblastoma have high levels of ctDNA, especially at the time of diagnosis and relapse, and tumor‐specific genomic alterations have reliably been detected in sera from these children, including MYCN amplification, gain of chromosome 17q, and (most recently) ALK mutations using a droplet digital polymerase chain reaction system . Although potentially useful for monitoring disease burden and response to treatment, the real therapeutic potential of detecting ctDNA may be in the setting of relapsed neuroblastoma, in which the acquisition of actionable somatic aberrations may have been acquired through clonal evolution and may represent a therapeutic opportunity to initiate targeted therapy in these patients, as discussed above.…”

“…121,122 It has been observed that children with neuroblastoma have high levels of ctDNA, especially at the time of diagnosis and relapse, and tumor-specific genomic alterations have reliably been detected in sera from these children, including MYCN amplification, gain of chromosome 17q, and (most recently) ALK mutations using a droplet digital polymerase chain reaction system. [122][123][124][125][126] Although potentially useful for monitoring disease burden and response to treatment, the real therapeutic potential of detecting ctDNA may be in the setting of relapsed neuroblastoma, in which the acquisition of actionable somatic aberrations may have been acquired through clonal evolution and may represent a therapeutic opportunity to initiate targeted therapy in these patients, as discussed above. Finally, the use of serial ctDNA detec-tion for prognostic purposes has not been studied in neuroblastoma but may also offer an opportunity to capitalize on this technology.…”

Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies

“…In one study of patients with MYCN ‐amplified neuroblastoma, MYCN was detected by real‐time PCR in plasma. The authors demonstrated that MYCN levels remained elevated in patients with subtotal resections, but returned to baseline levels in patients with complete resections . Wilms tumor has a genome with few recurrent mutations, but frequently has a characteristic aberrant methylation at 11p15.…”