Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma (2024)

van Wezel, E. M., Zwijnenburg, D., Zappeij-Kannegieter, L., Bus, E., van Noesel, M. M., Molenaar, J. J., Versteeg, R., Fiocco, M., Caron, H. N., van der Schoot, C. E., Koster, J., & Tytgat, G. A. M. (2015). Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma. Journal of Molecular Diagnostics, 17(1), 43-52. https://doi.org/10.1016/j.jmoldx.2014.09.005

van Wezel, Esther M ; Zwijnenburg, Danny ; Zappeij-Kannegieter, Lily et al. / Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma. In: Journal of Molecular Diagnostics. 2015 ; Vol. 17, No. 1. pp. 43-52.

@article{14371c3db0654941b35fc33e07dad3be,

title = "Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma",

abstract = "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. ",

keywords = "Antineoplastic Agents/therapeutic use, Biomarkers, Tumor/genetics, Bone Marrow/metabolism, Child, Child, Preschool, Chromosome Breakpoints, Female, Genetic Markers, Genome, Human, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Infant, Male, Neoplasm Staging, Neoplasm, Residual/drug therapy, Neuroblastoma/drug therapy, Real-Time Polymerase Chain Reaction/methods, Survival Analysis",

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

note = "Copyright {\textcopyright} 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.",

year = "2015",

month = jan,

doi = "10.1016/j.jmoldx.2014.09.005",

language = "English",

volume = "17",

pages = "43--52",

journal = "Journal of Molecular Diagnostics",

issn = "1525-1578",

publisher = "Elsevier",

number = "1",

}

van Wezel, EM, Zwijnenburg, D, Zappeij-Kannegieter, L, Bus, E, van Noesel, MM, Molenaar, JJ, Versteeg, R, Fiocco, M, Caron, HN, van der Schoot, CE, Koster, J & Tytgat, GAM 2015, 'Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma', Journal of Molecular Diagnostics, vol. 17, no. 1, pp. 43-52. https://doi.org/10.1016/j.jmoldx.2014.09.005

Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma. / van Wezel, Esther M; Zwijnenburg, Danny; Zappeij-Kannegieter, Lily et al.
In: Journal of Molecular Diagnostics, Vol. 17, No. 1, 01.2015, p. 43-52.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma

AU - van Wezel, Esther M

AU - Zwijnenburg, Danny

AU - Zappeij-Kannegieter, Lily

AU - Bus, Erik

AU - van Noesel, Max M

AU - Molenaar, Jan J

AU - Versteeg, Rogier

AU - Fiocco, Marta

AU - Caron, Huib N

AU - van der Schoot, C Ellen

AU - Koster, Jan

AU - Tytgat, Godelieve A M

N1 - Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

PY - 2015/1

Y1 - 2015/1

N2 - 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.

AB - 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.

KW - Antineoplastic Agents/therapeutic use

KW - Biomarkers, Tumor/genetics

KW - Bone Marrow/metabolism

KW - Child

KW - Child, Preschool

KW - Chromosome Breakpoints

KW - Female

KW - Genetic Markers

KW - Genome, Human

KW - Genome-Wide Association Study

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Infant

KW - Male

KW - Neoplasm Staging

KW - Neoplasm, Residual/drug therapy

KW - Neuroblastoma/drug therapy

KW - Real-Time Polymerase Chain Reaction/methods

KW - Survival Analysis

U2 - 10.1016/j.jmoldx.2014.09.005

DO - 10.1016/j.jmoldx.2014.09.005

M3 - Article

C2 - 25445214

SN - 1525-1578

VL - 17

SP - 43

EP - 52

JO - Journal of Molecular Diagnostics

JF - Journal of Molecular Diagnostics

IS - 1

ER -

van Wezel EM, Zwijnenburg D, Zappeij-Kannegieter L, Bus E, van Noesel MM, Molenaar JJ et al. Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma. Journal of Molecular Diagnostics. 2015 Jan;17(1):43-52. doi: 10.1016/j.jmoldx.2014.09.005