부산대학교 도서관

Neurofibromatosis type-1 (NF1) patients suffer from cutaneous and subcutaneous neurofibromas (CNF) and large plexiform neurofibromas (PNF). Whole gene deletions of the NF1 gene can cause a more severe phenotype compared to smaller intragenic changes. Two distinct groups of NF1 whole gene deletions are type-1 deletions and atypical deletions. Our aim was to assess volumes and averaged annual growth-rates of CNF and PNF in patients with NF1 whole gene deletions and to compare these with NF1 patients without large deletions of the NF1 gene. We retrospectively evaluated 140 whole-body MR examinations of 38 patients with NF1 whole gene deletions (type-1 group: n = 27/atypical group n = 11) and an age- and sex matched collective of 38 NF1-patients. Age-dependent subgroups were created (0–18 vs >18 years). Sixty-four patients received follow-up MRI examinations (NF1whole gene deletion n = 32/control group n = 32). Whole-body tumor-volumes were semi-automatically assessed (MedX, V3.42). Tumor volumes and averaged annual growth-rates were compared. Median tumor-burden was significantly higher in the type-1 group (418ml; IQR 77 – 950ml, p = 0.012) but not in the atypical group (356ml;IQR 140–1190ml, p = 0.099) when compared to the controls (49ml; IQR 11–691ml). Averaged annual growth rates were significantly higher in both the type-1 group (14%/year; IQR 45–36%/year, p = 0.004) and atypical group (11%/year; IQR 5–23%/year, p = 0.014) compared to the controls (4%/year; IQR1–8%/year). Averaged annual growth rates were significantly higher in pediatric patients with type-1 deletions (21%/year) compared with adult patients (8%/year, p = 0.014) and also compared with pediatric patients without large deletions of the NF1 gene (3.3%/year, p = 0.0015). NF1 whole gene deletions cause a more severe phenotype of NF1 with higher tumor burden and higher growth-rates compared to NF1 patients without large deletions of the NF1 gene. In particular, pediatric patients with type-1 deletions display a pronounced tumor growth. Author summary: Neurofibromatosis type-1 (NF1) is an autosomal dominantly inherited tumor predisposition syndrome and is caused by a variety of mutations of the NF1 gene. Large deletions encompassing the entire NF1 gene are known to be associated with a more severe clinical phenotype. A hallmark feature of NF1 is the development of different benign tumors: cutaneous or subcutaneous neurofibromas (CNF) and the potentially large plexiform neurofibromas (PNF). Importantly, PNF can undergo transformation into malignant peripheral nerve sheath tumors, which contribute to the increased mortality of NF1 patients. Identified risk factors for malignant transformation are NF1 whole gene deletions, large whole-body tumor burden and a high number of subcutaneous neurofibromas. We performed semi-automated volumetry of these tumors to determine volumes and growth rates of CNF and PNF in patients with whole gene deletions and a control group of NF1 patients without large deletions of the NF1 gene. Our results indicate that NF1 whole gene deletions lead to higher tumor burden and higher growth rates. In particular, pediatric NF1 patients with a specific type of whole gene deletion (type-1 deletion) exhibit rapid growth of PNF. We therefore suggest that these patients should be monitored in close intervals to evaluate tumor growth and risk of malignant transformation. [ABSTRACT FROM AUTHOR]