Somatic copy number alterations and mutation landscape in before and post-treatment malignant rhabdoid tumor

Background and objectives

Malignant rhabdoid tumor (MRT) is an aggressive malignancy driven by pathogenic variants of SMARCB1/INI1 or, rarely, SMARCA4/BRG1. The heterogeneity of MRT suggests that other genomic alterations might contribute to tumor behavior. This study aimed to evaluate somatic copy number alterations (SCNAs) and mutation landscapes in MRT before and after treatment.

Methods

With IRB approval, five patients underwent normal-tumor paired whole exome sequencing. Subsequently, the results were further analyzed using MuTect v1.1 for variant DNA and cn.mops for SCNA.

Results

Our study revealed recurrent SCNAs harboring genes known to be involved in tumorigenesis. These include 2q37.3 gain (4/5, 80%, programmed death 1, TWIST2), 7q32.1 gain (3/5, 60%), 11q12.2 gain (3/5, 60%), 14q32.3 gain (4/5, 80%), 19p13.2 loss (SMARCA4, 4/5, 80%), 21q22.3 gain (3/5, 60%), and 22q11.1 loss (2/5, 40%, involving SMARCB1). Alterations more common in posttreatment MRTs included 11p15.4 gain (3/3, 100%) and 11q12.2 gain (2/3, 67%). No actionable pathogenic variants were observed. PD-1 immunohistochemistry correlated with 2q37.3 gain.

Conclusions

Our study demonstrated that in addition to the driver mutations SMARCB1 and SMARCA4, MRT patients exhibit recurrent SCNAs. As demonstrated by PD-1 immunohistochemistry, the expression of genes within these chromosomal loci correlates with tumor progression. Nevertheless, genes within these regions may be worthy of further studies for their role in tumorigenesis and tumor progression including metastasis, their potential as treatment targets, and their response to treatment.

https://www.xiahepublishing.com/2771-165X/JCTP-2023-00028

The study was recently published in the Journal of Clinical and Translational Pathology.

Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.

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