Browsing by Author "Pillhofer, Gabriella Peta"

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    Germline Cancer Predisposition Variants in Paediatric Rhabdomyosarcoma
    (University of the Witwatersrand, Johannesburg, 2023) Pillhofer, Gabriella Peta; Lamola, Lindie; Mnika, Khuthala
    Rhabdomyosarcoma (RMS) is cancer that originates from undifferentiated skeletal muscle cells. RMS is the most common tissue sarcoma in children and adolescents and has over 50% of cases occurring in individuals under the age of 10 and thus there is reason to suspect that RMS may have a hereditary predisposition. However, much of the existing research of germline predisposition in paediatric RMS is focused on ethnically European populations, and currently very little data is available from African populations. In this study, we aimed to identify RMS predisposition variants by performing whole exome sequencing (WES) on germline DNA from eight paediatric patients diagnosed with RMS. Following WES, variant annotation and filtering was performed to identify variants in genes of interest that were potentially germline causes of malignancy. Filtered variants were then classified according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines. This study identified four variants of uncertain significance (VUSs) in four patients. Two of these were in genes that have previously been associated with an RMS phenotype (SDHB and BRCA1), and two were in genes that have been associated with a hereditary cancer syndrome that is not linked to RMS (CBL and CREBBP). While the highlighted variants are not of clinical significance, this study emphasises the importance of cataloguing and reporting VUSs in research in Africa. By expanding the genomic database on African patients, the analysis of variants on the continent may be made more accurate and efficient. It is the goal that the knowledge gained from this study will contribute to the information base of hereditary paediatric cancers in Africa, and that it may encourage similar research so that the field may continue to expand.