Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma

Esther M van Wezel, Danny Zwijnenburg, Lily Zappeij-Kannegieter, Erik Bus, Max M van Noesel, Jan J Molenaar, Rogier Versteeg, Marta Fiocco, Huib N Caron, C Ellen van der Schoot, Jan Koster, Godelieve A M Tytgat

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

PCR-based detection of minimal residual disease (MRD) in neuroblastoma is currently based on RNA markers; however, expression of these targets can vary, and only paired-like homeobox 2b has no background expression. We investigated whether chromosomal breakpoints, identified by whole-genome sequencing (WGS), can be used as patient-specific DNA MRD markers. WGS data were used to develop large numbers of real-time PCRs specific for tumors of eight patients. These PCRs were used to quantify chromosomal breakpoints in primary tumor and bone marrow samples. Finally, the DNA breakpoints with the highest abundance were compared with a panel of RNA markers. By WGS we identified 42 chromosomal breakpoints in tumor samples from eight patients and developed specific quantitative real-time PCRs for each breakpoint. The tumor-specific breakpoints were all present in bone marrow at diagnosis. For one patient slight clonal selection was observed in response to treatment. Positivity of DNA MRD markers preceded disease progression in four of five patients; in one patient the RNA markers remained negative. For 16 of 22 samples MRD levels determined by RNA and DNA were comparable and in 6 of 22 samples higher MRD levels were detected by DNA markers. DNA breakpoints used as MRD targets in neuroblastoma are reliable and stable markers. In addition, this technique might be applicable for detecting tumor cells in other types of cancer.

Originele taal-2Engels
Pagina's (van-tot)43-52
Aantal pagina's10
TijdschriftThe Journal of molecular diagnostics : JMD
Volume17
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - jan. 2015
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma'. Samen vormen ze een unieke vingerafdruk.

Citeer dit