Clonal diversity of recurrently mutated genes in myelodysplastic syndromes | Aplastic Anemia and MDS International Foundation

Clonal diversity of recurrently mutated genes in myelodysplastic syndromes

Journal Title: 
Leukemia
Author(s): 
Walter MJ, Shen D, Shao J, Ding L, White B, Kandoth C, Miller CA, Niu B, McLellan MD, Dees ND, Fulton R, Elliot K, Heath S, Grillot M, Westervelt P, Link DC, Dipersio JF, Mardis E, Ley TJ, Wilson RK, Graubert TA
Primary Author: 
Walter MJ
Original Publication Date: 
Wednesday, February 27, 2013

Recent studies suggest that most cases of myelodysplastic syndrome (MDS) are clonally heterogeneous, with a founding clone and multiple subclones. It is not known whether specific gene mutations typically occur in founding clones or subclones. We screened a panel of 94 candidate genes in a cohort of 157 patients with MDS or secondary acute myeloid leukemia (sAML). This included 150 cases with samples obtained at MDS diagnosis and 15 cases with samples obtained at sAML transformation (8 were also analyzed at the MDS stage). We performed whole genome sequencing (WGS) to define the clonal architecture in 8 sAML genomes and identified the range of variant allele frequencies (VAFs) for founding clone mutations. At least one mutation or cytogenetic abnormality was detected in 83% of the 150 MDS patients and 17 genes were significantly mutated with an FDR 0.05. Individual genes and patient samples displayed a wide range of VAFs for recurrently mutated genes, indicating that no single gene is exclusively mutated in the founding clone. The VAFs of recurrently mutated genes did not fully recapitulate the clonal architecture defined by WGS, suggesting that comprehensive sequencing may be required to accurately assess the clonal status of recurrently mutated genes in MDS.Leukemia accepted article preview online,

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