Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A

We describe recurrent chromothripsis and structural variation of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ~25% of patients (‘chr21amp’). Chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. Here we provide high-depth whole genome sequencing (WGS) in five chr21amp BP-MPN cases, to a median coverage of 81x [range 77-86] and purity 79% [range 58-88%].

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Publication

Publications	Citations
Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast-phase MPN through targetable overexpression of DYRK1A. Brierley CK, Yip BH, Orlando G, Wen J, Wen S, Goyal H, Levine M, Jakobsdottir GM, Tapinos A, Cornish AJ, Rodriguez-Romera A, Rodriguez-Meira A, Bashton M, Hamblin A, Clark SA, Hamley JC, Fox O, Giurgiu M, O'Sullivan J, Murphy L, Adamo A, Olijnik AA, Cotton A, Hendrix E, Narina S, Pruett-Miller SM, Enshaei A, Harrison C, Drummond M, Knapper S, Tefferi A, Antony-Debré I, Davies J, Henssen AG, Thongjuea S, Wedge DC, Constantinescu SN, Papaemmanuil E, Psaila B, Crispino JD, Mead AJ. Nat Genet 57: 2025 1478-1492	4

Publications

Citations

Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast-phase MPN through targetable overexpression of DYRK1A.
Brierley CK, Yip BH, Orlando G, Wen J, Wen S, Goyal H, Levine M, Jakobsdottir GM, Tapinos A, Cornish AJ, Rodriguez-Romera A, Rodriguez-Meira A, Bashton M, Hamblin A, Clark SA, Hamley JC, Fox O, Giurgiu M, O'Sullivan J, Murphy L, Adamo A, Olijnik AA, Cotton A, Hendrix E, Narina S, Pruett-Miller SM, Enshaei A, Harrison C, Drummond M, Knapper S, Tefferi A, Antony-Debré I, Davies J, Henssen AG, Thongjuea S, Wedge DC, Constantinescu SN, Papaemmanuil E, Psaila B, Crispino JD, Mead AJ. Nat Genet 57: 2025 1478-1492