Gene expression profiling and hierarchical clustering analysis

Gene expression profiles of 14 leiomyomas from four HLRCC patients and three FH-deficient sporadic tumours and their corresponding normal myometrial tissue samples were analysed together with 58 uterine leiomyomas and corresponding normal samples from which we had both expression and whole-genome sequencing data in-house (19 MED12 mutation-positive and 39 MED12 and FH wild-type tumours) (Mehine et al, 2013, 2016). Gene expression data was constructed using Affymetrix GeneChip Human Exon 1.0 ST Arrays (Affymetrix) at the Biomedicum Functional Genomics Unit, Helsinki, Finland. The expression data was analysed with Partek Genomic Suite v. 6.5 (Partek Incorporated, St Louis, MO, USA) using re-mapped Brainarray Custom CDF files (HuEx10stv2_Hs_ENSG, Version 16). All samples were quantile-normalised by the Robust Multichip Average method and adjusted for probe sequence and GC-content. Unsupervised hierarchical clustering analysis (Cosine dissimilarity) was performed with 1% most variable genes (n=372), defined by the coefficient of variation calculated across all tumour samples.