Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects ofSF3B1mutations DOI
Alicja Pacholewska, Matthias Lienhard, Mirko Brüggemann

и другие.

Genome Research, Год журнала: 2024, Номер 34(11), С. 1832 - 1848

Опубликована: Сен. 13, 2024

Mutations in splicing factor 3B subunit 1 ( SF3B1 ) frequently occur patients with chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDSs). These mutations have different effects on the disease prognosis beneficial effect MDS worse CLL patients. A full-length transcriptome approach can expand our knowledge mutation RNA its contribution to patient survival treatment options. We applied long-read sequencing (LRTS) 44 patients, as well two pairs of isogenic cell lines without mutations, found >60% novel isoforms. Splicing alterations were largely shared between cancer types specifically affected usage introns 3′ splice sites. Our data highlighted a constrained window at canonical sites which dynamic splice-site switches occurred -mutated Using transcriptome-wide RNA-binding maps molecular dynamics simulations, we showed multimodal binding predicted reduced second pocket K700E . work presents hitherto most-complete LRTS study provides resource aberrant cancer. Moreover, that prognosises result most likely from expanded during carcinogenesis rather than mechanisms action mutated SF3B1. results important implications for understanding role hematological malignancies other related diseases.

Язык: Английский

Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects ofSF3B1mutations DOI
Alicja Pacholewska, Matthias Lienhard, Mirko Brüggemann

и другие.

Genome Research, Год журнала: 2024, Номер 34(11), С. 1832 - 1848

Опубликована: Сен. 13, 2024

Mutations in splicing factor 3B subunit 1 ( SF3B1 ) frequently occur patients with chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDSs). These mutations have different effects on the disease prognosis beneficial effect MDS worse CLL patients. A full-length transcriptome approach can expand our knowledge mutation RNA its contribution to patient survival treatment options. We applied long-read sequencing (LRTS) 44 patients, as well two pairs of isogenic cell lines without mutations, found >60% novel isoforms. Splicing alterations were largely shared between cancer types specifically affected usage introns 3′ splice sites. Our data highlighted a constrained window at canonical sites which dynamic splice-site switches occurred -mutated Using transcriptome-wide RNA-binding maps molecular dynamics simulations, we showed multimodal binding predicted reduced second pocket K700E . work presents hitherto most-complete LRTS study provides resource aberrant cancer. Moreover, that prognosises result most likely from expanded during carcinogenesis rather than mechanisms action mutated SF3B1. results important implications for understanding role hematological malignancies other related diseases.

Язык: Английский

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