A molecular phenotypic map of Malignant Pleural Mesothelioma

Background Malignant Pleural Mesothelioma (MPM) is a rare understudied cancer associated with exposure to asbestos. So far, MPM patients have benefited marginally from the genomics medicine revolution due to the limited size or breadth of existing molecular studies. In the context of the MESOMICS project, we have performed the most comprehensive molecular characterization of MPM to date, with the underlying dataset made of the largest whole genome sequencing series yet reported, together with transcriptome sequencing and methylation arrays for 120 MPM patients. Results We first provide comprehensive quality controls for all samples, of both raw and processed data. Due to the difficulty in collecting specimens from such rare tumors, a part of the cohort does not include matched normal material. We provide a detailed analysis of data processing of these tumor-only samples, showing that all somatic alteration calls match very stringent criteria of precision and recall. Finally, integrating our data with previously published multi-omic MPM datasets ( n = 374 in total), we provide an extensive molecular phenotype map of MPM based on the multi-task theory. The generated map can be interactively explored and interrogated on the UCSC TumorMap portal (). Conclusions This new high quality MPM multi-omics dataset, together with the state-of-art bioinformatics and interactive visualization tools we provide, will support the development of precision medicine in MPM that is particularly challenging to implement in rare cancers due to limited molecular studies. ### Competing Interest Statement Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organisation, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organisation. * ABRA : Assembly-Based Realigner BAM : Binary Alignment Map CDS : coding sequence CNV : Copy Number Variant CpG : cytosine–phosphate–guanine EGA : European Genome-phenome Archive EMBL-EBI : European Bioinformatics Institute GATK : Genome Analysis Toolkit IARC : International Agency for Research on Cancer MME : malignant mesothelioma epithelioid MMB : malignant mesothelioma biphasic MMS : malignant mesothelioma sarcomatoid MPM : malignant pleural mesothelioma PCA : principal component analysis QC : quality control FR : Random Forest RNA-Seq : RNA sequencing SNP : single-nucleotide polymorphism STAR : Spliced Transcripts Alignment to a Reference TES : transcription end site TSS : transcription start site UCSC : University of California Santa Cruz SV : Structural Variant vst : variance-stabilized transformation WGS : whole-genome sequencing