Researchers Develop Targeted Next-Generation Sequencing Assay for Myeloid Neoplasms

Researchers from South Korea said they have developed a next-generation sequencing (NGS) assay to detect somatic mutations, translocations, and germline mutations in a single assay for the purpose of supplementing or replacing conventional tests in patients with myeloid neoplasms.

Writing in a recent issue of PLoS One, the researchers said were able to discover a high frequency of germline mutations in cancer predisposition genes. Patients with these mutations exhibited different clinical characteristics, suggesting that germline predisposition has significant clinical implications.

Other whole genome and exome studies have revealed a wide genetic heterogeneity in myeloid neoplasm by discovering oncogenic mutations in hundreds of genes, the authors explained.

They noted that the 2016 World Health Organization revised classification of myeloid neoplasms and acute leukemia introduced a number of genes with somatic mutations and a category for germline predisposition syndromes in myeloid neoplasms for use in classifying cases with an inherited defect.

Compared with conventional tests, NGS testing can identify a number of mutations that are critical for diagnosis and risk stratification in a relatively short time. Conventional testing methods, such as fluorescence in situ hybridization and reverse transcription polymerase chain reaction, can be used to detect various type of genetic variations, including structural variations.

The NGS assay developed by the researchers covers genes for most germline predisposition syndromes and intronic hotpots of 12 recurrently translocated genes. They conducted extensive bioinformatics analyses, such as by recycling off-target data to analyze whole-genome copy number status, which could supplement conventional cytogenetics.

The researchers analyzed bone marrow aspirates of patients diagnosed with acute myeloid leukemia, myelodysplastic syndrome, and myeloproliferative neoplasm between July 2016 and May 2017. They found that 8.4% to 11.6% of patients with acute myeloid leukemia and 12.9% of patients with myeloproliferative neoplasms had germline mutations, and most were heterozygous carriers for autosomal recessive marrow failure syndromes. These patients often did not respond to standard chemotherapy, suggesting that germline predisposition may have distinct and significant clinical implications.

Reference

KimB, Lee H, Jang J, et al. Targeted next generation sequencing can serve as an alternative to conventional tests in myeloid neoplasms [published online March 6, 2019]. PLoS One. doi: 10.1371/journal.pone.0212228.