Atypical teratoid rhabdoid tumor in a child with neurofibromatosis type 2: A novel dual diagnosis

• Published in: Cancer genetics Vol. 262-263; pp. 1 - 4
• Main Authors: Kotch, Chelsea, Fisher, Michael J, Lin, Fumin, Zhong, Yiming, Gallo, Dan, Fan, Zhiqian, Chen, Jiani, Santi, Mariarita, Li, Marilyn M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2022
• Subjects: Atypical teratoid rhabdoid tumor; Central Nervous System Neoplasms - genetics; Child, Preschool; Homozygote; Humans; Neoplasms, Neuroepithelial - genetics; Neurofibromatosis 2 - genetics; Neurofibromatosis type 2; Next generation sequencing; Rhabdoid Tumor - genetics; Rhabdoid Tumor - pathology; Sequence Deletion; SMARCB1 Protein - genetics; Teratoma - genetics; Teratoma - pathology; Next generation sequencing; Atypical teratoid rhabdoid tumor; Neurofibromatosis type 2
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2021.12.004

•Pathogenic germline NF2 mutation was identified in a patient with atypical teratoid rhabdoid tumor.•Chromosome with germline deletion of NF2 acquired a somatic SMARCB1 deletion followed by chr22 LOH.•Cascade represents a novel “four-hit” mechanism of SMARCB1 inactivation resulting in ATRT.
Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by the development of tumors of the nervous system and is associated with NF2 gene alterations. Atypical teratoid rhabdoid tumor (ATRT) is a malignant central nervous system tumor that occurs primarily in children less than 3 years of age. The majority of cases of ATRT demonstrate genomic alterations of SMARCB1, a core member of the SWI/SNF chromatin-remodeling complex and tumor suppressor gene. SMARCB1 inactivation in ATRT is occasionally associated with somatic NF2 deletion; however, concurrent germline NF2 mutations have not been reported. Herein, we describe the case of a 3-year-old patient who presented with an intracranial mass. Next generation sequencing analysis of tumor identified homozygous deletions of the entire SMARCB1 gene and exon 7 to exon 14 of NF2 gene with whole chromosome 22 loss of heterozygosity (LOH). Multiplex Ligation-dependent Probe Amplification (MLPA) assay performed on blood identified a germline heterozygous intragenic deletion of NF2 exon 7 to exon 14; a somatic chromosome 22 LOH led to the homozygous deletion. SMARCB1 MLPA assay of blood showed no deletion. This cascade represents a novel, “four-hit” mechanism of SMARCB1 inactivation resulting in ATRT and the first known dual diagnosis of NF2 and ATRT.