{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:00:53Z","timestamp":1792000853472,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T00:00:00Z","timestamp":1560470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Schornsteinfeger helfen krebskranken Kindern"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Quantification of tumour\u2010specific molecular markers at the RNA and DNA level for treatment response monitoring is crucial for risk\u2010adapted stratification and guidance of individualized therapy in leukaemia and other malignancies. Most pediatric leukaemias and solid tumours of mesenchymal origin are characterized by a relatively low mutation burden at the single nucleotide level and the presence of recurrent chromosomal translocations. The genomic fusion sites resulting from translocations are stable molecular tumour markers; however, repeat\u2010rich DNA sequences flanking intronic breakpoints limit the design of high sensitivity PCR assays for minimal residual disease (MRD) monitoring. Here, we quantitatively evaluated the impact of repeat elements on assay selection and the feasibility of using extended amplicons (\u22641330\u00a0bp) amplified by droplet digital PCR to monitor pediatric chronic myeloid leukaemia (CML). Molecular characterization of 178 genomic\n                    <jats:italic>BCR\u2010ABL1<\/jats:italic>\n                    fusion sites showed that 64% were located within sequence repeat elements, impeding optimal primer\/probe design. Comparative quantification of DNA and RNA\n                    <jats:italic>BCR\u2010ABL1<\/jats:italic>\n                    copy numbers in 687 specimens from 55 pediatric patients revealed that their levels were highly correlated. The combination of droplet digital PCR, double quenched probes and extended amplicons represents a valuable tool for sensitive MRD assessment in CML and may be adapted to other translocation\u2010positive tumours.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.14321","type":"journal-article","created":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T07:01:27Z","timestamp":1560495687000},"page":"4955-4961","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Large amplicon droplet digital PCR for DNA\u2010based monitoring of pediatric chronic myeloid leukaemia"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4416-0394","authenticated-orcid":false,"given":"Manuela","family":"Krumbholz","sequence":"first","affiliation":[{"name":"Department of Pediatrics University Hospital Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Goerlitz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Hospital Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Hospital Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Hospital Erlangen Erlangen Germany"},{"name":"Department of Biology, Division of Genetics University of Erlangen\u2010Nuremberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meinolf","family":"Suttorp","sequence":"additional","affiliation":[{"name":"Medical Faculty, Pediatric Hemato\u2010Oncology Technical University Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4523-1676","authenticated-orcid":false,"given":"Markus","family":"Metzler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Hospital Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70233-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-483750"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12892"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0179-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2007.060112"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2007.085472"},{"key":"e_1_2_8_8_1","article-title":"Optimized digital droplet PCR for BCR\u2010ABL","author":"Maier J","year":"2018","journal-title":"J Mol 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