{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:28:20Z","timestamp":1784302100584,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institutes of Health","award":["R01 CA235026"],"award-info":[{"award-number":["R01 CA235026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Chronic lymphocytic leukemia (CLL) is characterized by multiple copy number alterations (CNAs) and somatic mutations that are central to disease prognosis, risk stratification, and mechanisms of therapy resistance. Fluorescence in situ hybridization (FISH) panels are widely used in clinical applications as the gold standard for screening prognostic chromosomal abnormalities in CLL. DNA sequencing is an alternative approach to identifying CNAs but is not an established method for clinical CNA screening. We sequenced DNA from 509 individuals with CLL or monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, using a targeted sequencing panel of 59 recurrently mutated genes in CLL and additional amplicons across regions affected by clinically relevant CNAs [i.e., del(17p), del(11q), del(13q), and trisomy 12]. We used the PatternCNV algorithm to call CNA and compared the concordance of calling clinically relevant CNAs by targeted sequencing to that of FISH. We found a high accuracy of calling CNAs via sequencing compared to FISH. With FISH as the gold standard, the specificity of targeted sequencing was &gt;95%, sensitivity was &gt;86%, positive predictive value was &gt;90%, and negative predictive value was &gt;84% across the clinically relevant CNAs. Using targeted sequencing, we were also able to identify other common CLL-associated CNAs, including del(6q), del(14q), and gain 8q, as well as complex karyotype, defined as the presence of 3 or more chromosomal abnormalities, in 26 patients. In a single and cost-effective assay that can be performed on stored DNA samples, targeted sequencing can simultaneously detect CNAs, somatic mutations, and complex karyotypes, which are all important prognostic features in CLL.<\/jats:p>","DOI":"10.3390\/cancers16132450","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T12:28:48Z","timestamp":1720009728000},"page":"2450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Utility of Targeted Sequencing Compared to FISH for Detection of Chronic Lymphocytic Leukemia Copy Number Alterations"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9434-5269","authenticated-orcid":false,"given":"J. Erin","family":"Wiedmeier-Nutor","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal E.","family":"McCabe","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9851-6897","authenticated-orcid":false,"given":"Erik","family":"Jessen","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Bonolo de Campos","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Boddicker","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie","family":"Griffin","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristine","family":"Allmer","sequence":"additional","affiliation":[{"name":"Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7313-1875","authenticated-orcid":false,"given":"Kari G.","family":"Rabe","sequence":"additional","affiliation":[{"name":"Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-178X","authenticated-orcid":false,"given":"James R.","family":"Cerhan","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer A.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5951-5055","authenticated-orcid":false,"given":"Neil E.","family":"Kay","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihuang","family":"Yan","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Van Dyke","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Slager","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Braggio","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/bjh.13933","article-title":"The Dohner fluorescence in situ hybridization prognostic classification of chronic lymphocytic leukaemia (CLL): The CLL Research Consortium experience","volume":"173","author":"Werner","year":"2016","journal-title":"Br. 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