Sézary Syndrome Shows Whole Genome Duplication as a Late Event in Tumor Evolution

Hain, Carsten; Stadler, Rudolf; Kalinowski, Jörn

doi:10.1016/j.jid.2021.11.009

Cited by 2 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is an extremely important point for further research in MF as a whole, as CTCL does not show highly recurrent SNVs but strong recurrence in CNVs, highlighting the great importance of CNVs in CTCL [ 20 ]. This fits with our previous analysis suggesting that CNVs are among the earliest mutations in the pathogenesis of SS [ 50 ]. For the ongoing endeavor to build genomic knowledge of the currently underrepresented early-stage MF and potentially discern progressing from indolent forms, the following points have to be considered.…”

Section: Resultssupporting

confidence: 93%

See 1 more Smart Citation

Unraveling the Structural Variations of Early-Stage Mycosis Fungoides—CD3 Based Purification and Third Generation Sequencing as Novel Tools for the Genomic Landscape in CTCL

Hain

Stadler

Kalinowski

2022

Cancers

Self Cite

View full text Add to dashboard Cite

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL). At present, knowledge of genetic changes in early-stage MF is insufficient. Additionally, low tumor cell fraction renders calling of copy-number variations as the predominant mutations in MF challenging, thereby impeding further investigations. We show that enrichment of T cells from a biopsy of a stage I MF patient greatly increases tumor fraction. This improvement enables accurate calling of recurrent MF copy-number variants such as ARID1A and CDKN2A deletion and STAT5 amplification, undetected in the unprocessed biopsy. Furthermore, we demonstrate that application of long-read nanopore sequencing is especially useful for the structural variant rich CTCL. We detect the structural variants underlying recurrent MF copy-number variants and show phasing of multiple breakpoints into complex structural variant haplotypes. Additionally, we record multiple occurrences of templated insertion structural variants in this sample. Taken together, this study suggests a workflow to make the early stages of MF accessible for genetic analysis, and indicates long-read sequencing as a major tool for genetic analysis for MF.

show abstract

Section: Resultssupporting

confidence: 93%

“…Short-read data processing and detection of somatic single nucleotide variants and copy-number variants was carried out as previously described [ 50 ]. In addition to the gatk-somatic-cnvs pipeline from GATK 4.1.4.0 [ 51 ], CNV calling was performed with CNVkit 0.9.10 [ 52 ] or CONTRA 2.0.8 [ 53 ] using standard parameters.…”

Section: Methodsmentioning

confidence: 99%