Clinical implications of copy number alteration detection using panel-based next-generation sequencing data in myelodysplastic syndrome.

Survival curves based on the number of genes with copy number alterations (CNAs) per patient. (A) Overall survival; (B) Acute myeloid leukemia-free survival. [Display omitted] • About 25% of MDS patients had at least one copy number alteration (CNA) with assaying 28 genes by NGS-based technologies. • The higher number of genes with CNAs per patient was significantly associated with inferior overall and leukemia-free survival. • By adding CNAs to somatic mutations, genetic alterations of TET2, LAMB4, U2AF1, and CBL showed a significant impact on survival. • Our results suggest the clinical usefulness of CNA detection using panel-based NGS data in MDS. Recent advancements in next-generation sequencing (NGS) technologies allow the simultaneous identification of targeted copy number alterations (CNAs) as well as somatic mutations using the same panel-based NGS data. We investigated whether CNAs detected by the targeted NGS data provided additional clinical implications, over somatic mutations, in myelodysplastic syndrome (MDS). Targeted deep sequencing of 28 well-known MDS-related genes was performed for 266 patients with MDS. Overall, 215 (80.8 %) patients were found to have at least one somatic mutation; 67 (25.2 %) had at least one CNA; 227 (85.3 %) had either a somatic mutation or CNA; and 12 had CNA without somatic mutations. Considering the clinical variables and somatic mutations alone, multivariate analysis demonstrated that sex, revised International Prognostic Scoring System (IPSS-R), and NRAS and TP53 mutations were independent prognostic factors for overall survival. For AML-free survival, these factors were sex, IPSS-R, and mutations in NRAS , DNMT3A , and complex karyotype/ TP53 mutations. When we consider clinical variables along with somatic mutations and CNAs, genetic alterations in TET2 , LAMB4 , U2AF1 , and CBL showed additional significant impact on the survivals. In conclusion, our study suggests that the concurrent detection of somatic mutations and targeted CNAs may provide clinically useful information for the prognosis of MDS patients. [ABSTRACT FROM AUTHOR]

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