The prognostic significance of global aberrant alternative splicing in patients with myelodysplastic syndrome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-08

AUTHORS

Yi-Tsung Yang, Yu-Chiao Chiu, Chein-Jun Kao, Hsin-An Hou, Chien-Chin Lin, Cheng-Hong Tsai, Mei-Hsuan Tseng, Wen-Chien Chou, Hwei-Fang Tien

ABSTRACT

Aberrant alternative splicing (AS) is a hallmark of cancer development. However, there are limited data regarding its clinical implications in myelodysplastic syndrome (MDS). In this study, we performed an in-depth analysis of global AS in 176 primary MDS patients with 20 normal marrow transplant donors as reference. We found that 26.9% of the expressed genes genome-wide were aberrantly spliced in MDS patients compared with normal donors. These aberrant AS genes were related to pathways involved in cell proliferation, cell adhesion and protein degradation. A higher degree of global aberrant AS was associated with male gender and U2AF1 mutation, and predicted shorter overall survival and time to leukemic change. Moreover, it was an independent unfavorable prognostic factor irrespective of age, revised international prognostic scoring system (IPSS-R) risk, and mutations in SRSF2, ZRSR2, ASXL1, TP53, and EZH2. With LASSO-Cox regression method, we constructed a simple prognosis prediction model composed of 13 aberrant AS genes, and demonstrated that it could well stratify MDS patients into distinct risk groups. To our knowledge, this is the first report demonstrating significant prognostic impacts of aberrant splicing on MDS patients. Further prospective studies in larger cohorts are needed to confirm our observations. More... »

PAGES

78

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41408-018-0115-2

    DOI

    http://dx.doi.org/10.1038/s41408-018-0115-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106125890

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30104611


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