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In this report we describe a patient with CLL, who developed a clonally\u2010related pleomorphic highly\u2010aggressive mantle cell lymphoma (MCL) after five cycles of a fludarabine\u2010based second\u2010line therapy for the first relapse of CLL. Molecular cytogenetic methods together with whole\u2010exome sequencing revealed numerous gene alterations restricted to the MCL clone (apart from the canonical t(11;14)(q13;q32) translocation) including gain of one copy of <jats:italic>ATM<\/jats:italic> gene or emergence of <jats:italic>TP53<\/jats:italic>, <jats:italic>CREBBP<\/jats:italic>, <jats:italic>NUP214<\/jats:italic>, <jats:italic>FUBP1<\/jats:italic> and <jats:italic>SF3B1<\/jats:italic> gene mutations. Similarly, gene expression analysis revealed vast differences between the MCL and CLL transcriptome, including overexpression of cyclin D1, downregulation of cyclins D2 and D3, or downregulation of <jats:italic>IL4R<\/jats:italic> in the MCL clone. Backtracking analysis using quantitative PCR specifically detecting an MCL\u2010restricted focal deletion of <jats:italic>TP53<\/jats:italic> revealed that the pre\u2010MCL clone appeared in the bone marrow and peripheral blood of the patient approximately 4 years before the clinical manifestation of MCL. Both molecular cytogenetic and sequencing data support the hypothesis of a slow development of the pre\u2010MCL clone in parallel to CLL over several years, and thereby exclude the possibility that the transformation event occurred at the stage of the CLL relapse clone by mere t(11;14)(q13;q32) acquisition.<\/jats:p>","DOI":"10.1002\/ijc.30263","type":"journal-article","created":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T02:26:51Z","timestamp":1468376811000},"page":"2252-2260","source":"Crossref","is-referenced-by-count":14,"title":["Mantle cell lymphoma\u2010variant Richter syndrome: Detailed molecular\u2010cytogenetic and backtracking analysis reveals slow evolution of a pre\u2010MCL clone in parallel with CLL over several years"],"prefix":"10.1002","volume":"139","author":[{"given":"Pavel","family":"Klener","sequence":"first","affiliation":[{"name":"Department of Hematology Charles University General Hospital Prague Prague Czech Republic"},{"name":"Institute of Pathological 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