Integrative multi-omics identifies high risk multiple myeloma subgroup associated with significant DNA loss and dysregulated DNA repair and cell cycle pathways

Autor: María Ortiz-Estévez, Fadi Towfic, Erin Flynt, Nicholas Stong, In Sock Jang, Kai Wang, Matthew W. B. Trotter, Anjan Thakurta
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: BMC Medical Genomics, Vol 14, Iss 1, Pp 1-14 (2021)
Druh dokumentu: article
ISSN: 1755-8794
DOI: 10.1186/s12920-021-01140-5
Popis: Abstract Background Despite significant therapeutic advances in improving lives of multiple myeloma (MM) patients, it remains mostly incurable, with patients ultimately becoming refractory to therapies. MM is a genetically heterogeneous disease and therapeutic resistance is driven by a complex interplay of disease pathobiology and mechanisms of drug resistance. We applied a multi-omics strategy using tumor-derived gene expression, single nucleotide variant, copy number variant, and structural variant profiles to investigate molecular subgroups in 514 newly diagnosed MM (NDMM) samples and identified 12 molecularly defined MM subgroups (MDMS1-12) with distinct genomic and transcriptomic features. Results Our integrative approach let us identify NDMM subgroups with transversal profiles to previously described ones, based on single data types, which shows the impact of this approach for disease stratification. One key novel subgroup is our MDMS8, associated with poor clinical outcome [median overall survival, 38 months (global log-rank p-value 9% of entire genome, t-test p value
Databáze: Directory of Open Access Journals
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