Mutational Spectrum of Myelodysplastic Syndrome Malignancies Revealed by Whole Exome Sequencing

• Published in: Blood 2012-11, Vol.120 (21), p.307-307
• Main Authors: Gómez-Seguí, Inés, Przychodzen, Bartlomiej P, Yoshida, Kenichi, Ruffalo, Matthew, Jerez, Andres, Makishima, Hideki, Miyano, Satoru, Shiraishi, Yuichi, Husseinzadeh, Holleh D, Evans, Edward P, Hosono, Naoko, Guinta, Kathryn M, LaFramboise, Thomas, Ogawa, Seishi, Saunthararajah, Yogen, Sekeres, Mikkael A., Maciejewski, Jaroslaw P.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V120.21.307.307

Abstract 307 Whole-exome (WES) sequencing revealed tremendous mutational heterogeneity in leukemia. While WES can be applied for discovery, it also has potential as a diagnostic tool that can overcome the shortcomings of current methods. We theorized that, in addition to mutation discovery, systematic application of WES in MDS may reveal distinct mutational patterns allowing for new molecular classification. We performed WES in 116 paired exomes, including MDS (n=57), MDS/MPN (n=36), and sAML (n=23). We also included comparative analysis with pAML (N=202; TCGA), and other publicly available data for a total of 333 exomes; 10 patients were studied serially. Paired DNA (marrow/CD3+ cells) was subjected to WES, sequence-aligned by BW Aligner, and variants detected via GATK pipeline (Broad Institute). We used defined criteria to minimize false-positives: P