Molecular Heterogeneity in Pediatric Malignant Rhabdoid Tumors in Patients With Multi-Organ Involvement.

Autor:	Miller KE; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States., Wheeler G; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., LaHaye S; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., Schieffer KM; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, United States., Cearlock S; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., Venkata LPR; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., Bravo AO; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., Grischow OE; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., Kelly BJ; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States., White P; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States., Pierson CR; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, United States.; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, United States.; Department of Biomedical Education and Anatomy, Division of Anatomy, The Ohio State University College of Medicine, Columbus, OH, United States., Boué DR; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, United States.; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, United States., Koo SC; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, United States., Klawinski D; Division of Hematology, Oncology, and Bone Marrow Transplant, Nationwide Children's Hospital, Columbus, OH, United States.; Pediatric Neuro-Oncology Program, Nationwide Children's Hospital, Columbus, OH, United States., Ranalli MA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.; Division of Hematology, Oncology, and Bone Marrow Transplant, Nationwide Children's Hospital, Columbus, OH, United States., Shaikhouni A; Department of Neurosurgery, Nationwide Children's Hospital, Columbus, OH, United States.; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, United States., Salloum R; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.; Division of Hematology, Oncology, and Bone Marrow Transplant, Nationwide Children's Hospital, Columbus, OH, United States.; Pediatric Neuro-Oncology Program, Nationwide Children's Hospital, Columbus, OH, United States., Shatara M; The Division of Hematology and Oncology, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO, United States., Leonard JR; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.; Department of Neurosurgery, Nationwide Children's Hospital, Columbus, OH, United States.; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, United States., Wilson RK; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States., Cottrell CE; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, United States., Mardis ER; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, United States., Koboldt DC; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Jul 13; Vol. 12, pp. 932337. Date of Electronic Publication: 2022 Jul 13 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.932337
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Miller, Wheeler, LaHaye, Schieffer, Cearlock, Venkata, Bravo, Grischow, Kelly, White, Pierson, Boué, Koo, Klawinski, Ranalli, Shaikhouni, Salloum, Shatara, Leonard, Wilson, Cottrell, Mardis and Koboldt.)
Databáze:	MEDLINE
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