SMARCA4-deficient primary bone sarcoma with "teratoid" features in a rhabdoid tumor predisposition syndrome patient

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• SMARCA4 is a key component of the SWI/SNF complex, and its germline pathogenic variants (PVs) are linked to rhabdoid tumor predisposition syndrome type 2 (RTPS2).
• RTPS2 is associated with specific cancers like ovarian small cell carcinoma (SCCOHT) and pediatric rhabdoid tumors.
• Primary bone neoplasms with SMARCA4 loss have not been previously documented.

Purpose of the Study:

• To describe a novel case of a primary bone sarcoma with SMARCA4 deficiency.
• To investigate the genetic basis of the observed SMARCA4 loss in the tumor.
• To expand the understanding of SMARCA4-associated tumor spectrum and its implications for hereditary cancer syndromes.

Main Methods:

• Histopathological examination of a primary high-grade femur sarcoma.
• Immunohistochemical analysis for SMARCA4 expression.
• Germline DNA sequencing to identify SMARCA4 pathogenic variants.
• Tumor genetic analysis to assess for loss of heterozygosity.

Main Results:

• A primary high-grade sarcoma with teratocarcinosarcoma-like features was identified in a 13-year-old patient.
• The tumor exhibited diffuse loss of SMARCA4 immunoexpression.
• A heterozygous nonsense SMARCA4 PV was detected in the patient's germline, with copy-neutral loss of heterozygosity in the tumor.

Conclusions:

• This case represents the first reported primary bone neoplasm with SMARCA4 loss.
• The findings broaden the spectrum of SMARCA4-deficient tumors.
• This expands the clinical implications for SMARCA4 germline tumor predisposition and the need for surveillance.