Li–Fraumeni-associated pancreatic neuroendocrine tumour and XAF1 p.Glu134Ter risk modifier variant

Abstract

Studies have demonstrated that up to 17% of patients with pancreatic neuroendocrine tumours (pNETs) present pathogenic germline variants (PGVs) in several different genes, irrespective of family cancer history. Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome related to PGVs in the TP53 gene. A previous case of a pNET associated with LFS (c.1009C > T, p.R337C) has been reported. Here we report the first case of a patient with pNET and TP53 p.R337H and XAF1 p.E134* germline variants, expanding the knowledge of LFS and germline mutations in neuroendocrine tumours.

Multiple TP53 p.R337H haplotypes and implications for tumor susceptibility

“…One such example is the p.R337H founder mutation that is common throughout southern Brazil, but in the context of two haplotypes that differ in the status of XAF1 and tumor susceptibility (Hap1 and Hap2). 8 , 41 , 42 As shown here, additional non-founder independent p.R337H alleles (Hap3-5) have been identified that also likely influence cancer risk. Therefore, genetic counselors and health care providers must be aware of these distinct p.R337H haplotypes and the potential implications of their associated differences on p53 expression, structure, and function, and consequently cancer risk.…”