IgCaller for reconstructing immunoglobulin gene rearrangements and oncogenic translocations from whole-genome sequencing in lymphoid neoplasms
Por:
Nadeu F., Mas-de-les-Valls R., Navarro A., Royo R., Martín S., Villamor N., Suárez-Cisneros H., Mares R., Lu J., Enjuanes A., Rivas-delgado A., Aymerich M., Baumann T., Colomer D., Delgado J., Morin R.D., Zenz T., Puente X.S., Campbell P.J., Beà S., Maura F., Campo E.
Publicada:
1 ene 2020
Resumen:
Immunoglobulin (Ig) gene rearrangements and oncogenic translocations are routinely assessed during the characterization of B cell neoplasms and stratification of patients with distinct clinical and biological features, with the assessment done using Sanger sequencing, targeted next-generation sequencing, or fluorescence in situ hybridization (FISH). Currently, a complete Ig characterization cannot be extracted from whole-genome sequencing (WGS) data due to the inherent complexity of the Ig loci. Here, we introduce IgCaller, an algorithm designed to fully characterize Ig gene rearrangements and oncogenic translocations from short-read WGS data. Using a cohort of 404 patients comprising different subtypes of B cell neoplasms, we demonstrate that IgCaller identifies both heavy and light chain rearrangements to provide additional information on their functionality, somatic mutational status, class switch recombination, and oncogenic Ig translocations. Our data thus support IgCaller to be a reliable alternative to Sanger sequencing and FISH for studying the genetic properties of the Ig loci. © 2020, The Author(s).
Filiaciones:
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
Barcelona Supercomputing Center (BSC), Barcelona, Spain
Hospital Clínic of Barcelona, Barcelona, Spain
Unitat de Genòmica, IDIBAPS, Barcelona, Spain
European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
Universitat de Barcelona, Barcelona, Spain
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada
Canada’s Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada
Department of Medical Oncology and Hematology, University Hospital and University of Zürich, Zürich, Switzerland
Departamento de Bioquímica Y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain
Wellcome Sanger Institute, Hinxton, Cambridgeshire, United Kingdom
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
All Open Access, Gold
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