Malignant rhabdoid tumors originating within and outside the central nervous system are clinically and molecularly heterogeneous

AbstractMultifocal synchronous or metachronous atypical teratoid rhabdoid tumors (ATRTs) and non-central nervous system malignant rhabdoid tumors (extra-CNS MRTs) are rare cancers. We reviewed the clinical and radiologic characteristics of affected patients seen at our institution. Genotyping and analysis of copy number abnormalities (CNAs) inSMARCB1 were performed in germline and tumor samples. Tumor samples underwent genome-wide DNA methylation and CNA analysis. The median age at diagnosis of 21 patients was 0.6  years. Two-thirds of ATRTs and extra-CNS MRTs were diagnosed synchronously. Although kidney tumors predominated, including two patients with bilateral involvement, at least 30% of cases lacked renal involvement. Histopathologic review confirmed MRTs in all cases and INI1 expression loss in all tum ors tested. Fourteen (78%) of 18 patients tested had heterozygous germlineSMARCB1 abnormalities. At least one allelicSMARCB1 abnormality was confirmed in 81 and 88% of ATRTs and extra-CNS MRTs, respectively. Unsupervised hierarchical clustering analysis of DNA methylation in 27 tumors and comparison with a reference group of 150 ATRTs classified the CNS tumors (n = 14) as sonic hedgehog (64%), tyrosinase (21%), and MYC (14%). The MYC subgroup accounted for 85% of 13 extra-CNS MRTs. Of 16 paired ATRTs and extra-CNS MRTs, the tumors in seven of eight patients showed a different pattern of genome-wide DNA methylation and/or CNAs suggestive of non-clonal orig in. CNS and e...
Source: Acta Neuropathologica - Category: Neurology Source Type: research