Methylation microarray-based detection of clinical copy-number aberrations in CLL benchmarked to standard FISH analysis

Dianna Hussmann; Anna Starnawska; Louise Kristensen; Iben Daugaard; Oriane Cédile; Vivi Quoc Nguyen; Tina E Kjeldsen; Christine Søholm Hansen; Jonas Bybjerg-Grauholm; Thomas Kristensen; Thomas Stauffer Larsen; Michael Boe Møller; Charlotte Guldborg Nyvold; Lise Lotte Hansen; Tomasz K Wojdacz

doi:10.1016/j.ygeno.2022.110510

Methylation microarray-based detection of clinical copy-number aberrations in CLL benchmarked to standard FISH analysis

Genomics. 2022 Nov;114(6):110510. doi: 10.1016/j.ygeno.2022.110510. Epub 2022 Oct 20.

Authors

Dianna Hussmann¹, Anna Starnawska², Louise Kristensen³, Iben Daugaard⁴, Oriane Cédile⁵, Vivi Quoc Nguyen³, Tina E Kjeldsen¹, Christine Søholm Hansen⁶, Jonas Bybjerg-Grauholm⁷, Thomas Kristensen⁸, Thomas Stauffer Larsen⁹, Michael Boe Møller¹⁰, Charlotte Guldborg Nyvold⁵, Lise Lotte Hansen¹, Tomasz K Wojdacz¹¹

Affiliations

¹ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
² Department of Biomedicine, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark; Centre for Genomics and Personalized Medicine, CGPM, Aarhus University, Aarhus, Denmark.
³ Department of Pathology, Odense University Hospital, Odense, Denmark.
⁴ Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
⁵ Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark.
⁶ The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark; Department of Psychiatry, Mount Sinai, New York, NY, USA.
⁷ The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
⁸ Department of Pathology, Odense University Hospital, Odense, Denmark; Department of Clinical Development, Odense University Hospital, Odense, Denmark.
⁹ Department of Haematology, Odense University Hospital, Odense, Denmark.
¹⁰ Department of Pathology, Odense University Hospital, Odense, Denmark; Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark.
¹¹ Department of Biomedicine, Aarhus University, Aarhus, Denmark; Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark; Independent Clinical Epigenetics Laboratory, Pomeranian Medical University, Szczecin, Poland. Electronic address: [email protected].

PMID: 36272495
DOI: 10.1016/j.ygeno.2022.110510

Abstract

Copy-number aberrations (CNAs) are assessed using FISH analysis in diagnostics of chronic lymphocytic leukemia (CLL), but CNAs can also be extrapolated from Illumina BeadChips developed for genome-wide methylation microarray screening. Increasing numbers of microarray data-sets are available from diagnostic samples, making it useful to assess the potential in CNA diagnostics. We benchmarked the limitations of CNA testing from two Illumina BeadChips (EPIC and 450k) and using two common packages for analysis (conumee and ChAMP) to FISH-based assessment of 11q, 13q, and 17p deletions in 202 CLL samples. Overall, the two packages predicted CNAs with similar accuracy regardless of the microarray type, but lower than FISH-based assessment. We showed that the bioinformatics analysis needs to be adjusted to the specific CNA, as no general settings were identified. Altogether, we were able to predict CNAs using methylation microarray data, however, with limited accuracy, making FISH-based assessment of deletions the superior diagnostic choice.

Keywords: 450k; CNA assessment; Chronic lymphocytic leukemia; Copy-number aberration; EPIC; Methylation microarray.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computational Biology
Humans
Leukemia, Lymphocytic, Chronic, B-Cell* / diagnosis
Leukemia, Lymphocytic, Chronic, B-Cell* / genetics