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We took advantage of an exome capture\u2010based RNA\u2010sequencing protocol to explore global gene expression in paired fresh\u2013frozen (FF) and FFPE samples from 16 diffuse large B\u2010cell lymphoma (DLBCL) patients. While FFPE samples generated fewer mapped reads compared to their FF counterparts, these reads captured the same library complexity and had a similar number of genes expressed on average. Furthermore, gene expression demonstrated a high correlation when comparing housekeeping genes only or across the entire transcriptome (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.99 for both comparisons). Differences in gene expression were primarily seen in lowly expressed genes and genes with small or large coding sequences. Using cell\u2010of\u2010origin classifiers and clinically relevant gene expression signatures for DLBCL, FF, and FFPE samples from the same biopsy paired nearly perfectly in clustering analysis. This was further confirmed in a validation cohort of 50 FFPE DLBCL samples. In summary, we found the biological differences between tumors to be far greater than artifacts created as a result of degraded RNA. We conclude that exome capture transcriptome sequencing data from archival samples can confidently be used for cell\u2010of\u2010origin classification of DLBCL samples.<\/jats:p>","DOI":"10.1002\/gcc.23002","type":"journal-article","created":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T03:05:24Z","timestamp":1634353524000},"page":"27-36","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transcriptome sequencing of archived lymphoma specimens is feasible and clinically relevant using exome capture technology"],"prefix":"10.1002","volume":"61","author":[{"given":"Aron","family":"Skaftason","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet 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