{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:28:19Z","timestamp":1790807299982,"version":"4.1.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Somatic hypermutation (SHM) status of the immunoglobulin heavy variable (IGHV) gene plays a crucial role in determining the prognosis and treatment of patients with chronic lymphocytic leukemia (CLL). A common approach for determining SHM status is multiplex polymerase chain reaction and Sanger sequencing of the immunoglobin heavy locus; however, this technique is low throughput, is vulnerable to failure, and does not allow multiplexing with other diagnostic assays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Here we designed and validated a DNA targeted capture approach to detect immunoglobulin heavy variable somatic hypermutation (IGHV SHM) status as a submodule of a larger next-generation sequencing (NGS) panel that also includes probes for ATM, BIRC3, CHD2, KLHL6, MYD88, NOTCH1, NOTCH2, POT1, SF3B1, TP53, and XPO1. The assay takes as input FASTQ files and outputs a report containing IGHV SHM status and V allele usage following European Research Initiative on CLL guidelines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We validated the approach on 35 CLL patient samples, 34 of which were characterized using Sanger sequencing. The NGS panel identified the IGHV SHM status of 34 of 35 CLL patients. We showed 100% sensitivity and specificity among the 33 CLL samples with both NGS and Sanger sequencing calls. Furthermore, we demonstrated that this panel can be combined with additional targeted capture panels to detect prognostically important CLL single nucleotide variants, insertions\/deletions, and copy number variants (TP53 copy number loss).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A targeted capture approach to IGHV SHM detection can be integrated into broader sequencing panels, allowing broad CLL prognostication in a single molecular assay.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvad147","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T16:24:15Z","timestamp":1704385455000},"page":"273-284","source":"Crossref","is-referenced-by-count":6,"title":["Chronic Lymphocytic Leukemia IGHV Somatic Hypermutation Detection by Targeted Capture Next-Generation Sequencing"],"prefix":"10.1093","volume":"70","author":[{"given":"Jennifer M","family":"Grants","sequence":"first","affiliation":[{"name":"Michael Smith Genome Sciences Centre, BC Cancer , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"May","sequence":"additional","affiliation":[{"name":"Michael Smith Genome Sciences Centre, BC Cancer , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Bridgers","sequence":"additional","affiliation":[{"name":"Michael Smith Genome Sciences Centre, BC Cancer , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Huang","sequence":"additional","affiliation":[{"name":"Michael Smith Genome Sciences Centre, BC Cancer , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3418-4958","authenticated-orcid":false,"given":"Sierra","family":"Gillis","sequence":"additional","affiliation":[{"name":"Michael Smith Genome Sciences Centre, BC Cancer , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Meissner","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer Centre , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merrill","family":"Boyle","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer Centre , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Ben-Neriah","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer Centre , Vancouver, BC , 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7146-7175","authenticated-orcid":false,"given":"Marco","family":"Marra","sequence":"additional","affiliation":[{"name":"Michael Smith Genome Sciences Centre, BC Cancer , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kridel","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre , Toronto, ON , Canada"},{"name":"Faculty of Medicine, University of Toronto , Toronto, ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J B","family":"Sabatini","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre , Toronto, ON , Canada"},{"name":"Department of Laboratory Medicine & Pathobiology, University of Toronto , Toronto, ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Steidl","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer Centre, Vancouver, BC, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Scott","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer Centre, Vancouver, BC, Canada"},{"name":"Department of Medicine, University of British Columbia , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-892X","authenticated-orcid":false,"given":"Aly","family":"Karsan","sequence":"additional","affiliation":[{"name":"Michael Smith Genome Sciences Centre, BC Cancer , Vancouver, BC , Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of British 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