Genome-wide DNA methylation profiling of SCCOHT and SMARCB1-mutated rhabdoid tumours

Extracranial rhabdoid tumours (ECRT) are an aggressive malignancy of infancy and early childhood. The vast majority of cases demonstrate inactivation of SMARCB1 (ECRT_SMARCB1) but, rarely, ECRT can harbour the alternative inactivation of SMARCA4 (ECRT_SMARCA4) instead of SMARCB1. To explore the place of ECRTSMARCA4 in the "rhabdoid tumour" spectrum, we generated and collected from previous studies genome-wide DNA methylation array data (n = 85) from Atypical/Teratoid Rhabdoid Tumours (ATRT), ECRT_SMARCB1, ECRT_SMARCA4 and small cell carcinomas of the ovary, hypercalcaemic type (SCCOHT) tumours. Using dimensionality reduction and unsupervised clustering approaches, our results demonstrate that ECRT_SMARCA4 display an intermediate DNA methylation profile between SCCOHT and ECRT_SMARCB1. Eighty five tumour samples were profiled using illumina Infinium Human EPIC Beadchip including 54 ATRTs (24 re-analyzed samples from Leruste et al., 2019), 13 ECRT_SMARCB1 (12 re-analyzed samples from Leruste et al., 2019), 9 ECRT_SMARCA4 (4 re-analyzed from Leruste et al., 2019; 5 re-analyzed from GSE161692: GSM4912763, GSM4912765, GSM4912764, GSM4912767, GSM4912768) and 9 SCCOHT samples. All previously published data included in our study (listed in the 'published_re-analyzed_data.xlsx') have been directly provided by the authors as IDAT files, and only 5 samples have the corresponding GEO records as indicated above.