An (epi-)genomics analysis of drug resistance in multiple myeloma


Multiple myeloma, a genetically highly heterogeneous type of cancer that forms in plasma cells, is the second most frequent hematologic malignancy. As is the case with many types of cancer, next-generation sequencing technologies have opened the door to great advances in the fight against multiple myeloma. There is increasing evidence, however, that many important genomic events, like certain types of structural variation or DNA base modifications, are harder or even impossible to study with short-read-based, next-generation sequencing technologies. Taking advantage of the latest advances in nanopore sequencing, we are studying the evolution of multiple myeloma using a collection of genomic approaches that are now more comprehensive, easier to perform, and cost-effective. We have sequenced three clinical cases that developed resistance to a variety of both standard treatments and novel immunotherapies, including one that has developed multi-drug resistance, as well as a multi-drug resistant cell line at different timepoints. The cases' diverse treatment histories and responses provide a unique opportunity to develop insights into the elusive mechanisms of drug resistance. This research aims at expanding our understanding of multiple myeloma, potentially propelling us towards more individualized treatment plans and innovative strategies to counteract drug resistance and improving overall therapeutic outcomes in the future.


Dr. Tomás Di Domenico is a computer scientist turned bioinformatician. After a PhD studying protein structure at the University of Padova in Italy, Tomás took a post-doctoral position at the University of Cambridge where he studied piRNAs, a type of non-coding RNAs that mostly targets transposable elements. This exposed him to the limitations of short-read sequencing approaches for repetitive regions and helped to discover the then upcoming long-read sequencing technologies. Since joining the MinION Access Program in 2014, Tomás has been a user of nanopore sequencing technology and he has closely followed its development. He currently works at the National Cancer Research Center in Spain and has introduced nanopore sequencing technology with the goal of furthering their ability to study and understand cancer.

Authors: Tomás Di Domenico