The landscape of somatic mutations in Down syndrome related myeloid disorders  

Oleh:

Yoshida, Kenichi ; Toki, Tsutomu ; Okuno, Yusuke ; Kanezaki, Rika ; Shiraishi, Yuichi

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 45 no. 11 (Nov. 2013), page 1293-1299.
Topik: Down syndrome; related myeloid disorders

Ketersediaan

Perpustakaan FK Nomor Panggil: N12.K Non-tandon: 1 (dapat dipinjam: 1) Tandon: tidak ada

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Isi artikel

Transient abnormal myelopoiesis (TAM) is a myeloid proliferation resembling acute megakaryoblastic leukemia (AMKL), mostly affecting perinatal infants with Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting AMKL after spontaneous remission DS-AMKL. Pathogenesis of these Down syndrome–related myeloid disorders is poorly understood, except for GATA1 mutations found in most cases. Here we report genomic profiling of 41 TAM, 49 DS-AMKL and 19 non-DS-AMKL samples, including whole-genome and/or whole-exome sequencing of 15 TAM and 14 DS-AMKL samples. TAM appears to be caused by a single GATA1 mutation and constitutive trisomy 21. Subsequent AMKL evolves from a pre-existing TAM clone through the acquisition of additional mutations, with major mutational targets including multiple cohesin components (53%), CTCF (20%), and EZH2, KANSL1 and other epigenetic regulators (45%), as well as common signaling pathways, such as the JAK family kinases, MPL, SH2B3 (LNK) and multiple RAS pathway genes (47%).

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