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Rhabdoid tumors (RTs) of the brain (atypical teratoid/rhabdoid tumor; AT/RT) and extracranial sites (most often the kidney; RTK) are malignant tumors predominantly occurring in children, frequently those with SMARCB1 germline alterations. Here we present data from seven RTs from three pediatric patients who all had multi-organ involvement. The tumors were analyzed using a multimodal molecular approach, which included exome sequencing of tumor and germline comparator and RNA sequencing and DNA array-based methylation profiling of tumors. SMARCB1 germline alterations were identified in all patients and in all tumors. We observed a second hit in SMARCB1 via chr22 loss of heterozygosity. By methylation profiling, all tumors were classified as rhabdoid tumors with a corresponding subclassification within the MYC, TYR, or SHH AT/RT subgroups. Using RNA-seq gene expression clustering, we recapitulated the classification of known AT/RT subgroups. Synchronous brain and kidney tumors from the same patient showed different patterns of either copy number variants, single-nucleotide variants, and/or genome-wide DNA methylation, suggestive of non-clonal origin. Furthermore, we demonstrated that a lung and abdominal metastasis from two patients shared overlapping molecular features with the patient’s primary kidney tumor, indicating the likely origin of the metastasis. In addition to the SMARCB1 events, we identified other whole-chromosome events and single-nucleotide variants in tumors, but none were found to be prognostic, diagnostic, or offer therapeutic potential for rhabdoid tumors. While our findings are of biological interest, there may also be clinical value in comprehensive molecular profiling in patients with multiple rhabdoid tumors, particularly given the potential prognostic and therapeutic implications for different rhabdoid tumor subgroups demonstrated in recent clinical trials and other large cohort studies.

Genome reduction has been widely studied in obligate intracellular bacterial mutualists of insects because they have, in comparison to closely-related, nonhost-associated bacteria, extremely small genomes. Pentatomid stinkbugs also maintain bacterial symbionts, yet they are extracellular, residing within host-derived crypts, and are transmitted to offspring outside of the host's tissues, which exposes them to the external environment. In this review, we explore how the multiphasic lifestyle of stinkbug symbionts (e.g., on the surfaces of eggs in various matrices during transmission and inside host-derived tissues during much of the host's life), in contrast with the solely intracellular lifestyle of many insect endosymbionts, may impact their genome's architecture, size and content. Furthermore, we demonstrate how additional stinkbug symbiont genomes are needed to more fully explore these questions and the potential value of the stinkbug-symbiont system in understanding genome evolution and reduction in the absence of intracellularity.