TSC2 rare germline variants in non-tuberous sclerosis patients with neuroendocrine neoplasias

    1. Jorge Sabbaga1,2
    1. 1Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil
    2. 2Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, São Paulo, Brazil
    3. 3Instituto de Biociências – Universidade de São Paulo (IB-USP), São Paulo, São Paulo, Brazil
    1. (Correspondence should be addressed to J Sabbaga: jsabbaga{at}uol.com.br)

    Dear Editor,

    Neuroendocrine neoplasias (NENs) represent a heterogeneous group of diseases with a wide spectrum of morbidity and lethality. These tumors can arise in almost any organ of the body, with the pancreas and the gastrointestinal tract being the most common primary sites (Yao et al. 2017). NENs are mainly considered sporadic diseases, although 5–20% of all cases occur in the context of genetic syndromes such as multiple endocrine neoplasia (MEN) type 1, MEN type 2, von Hippel–Lindau (VHL) disease, neurofibromatosis syndrome and tuberous sclerosis complex (TSC), which are caused by the presence of germline mutations in the MEN1, RET, VHL, NF1 and TSC1/TSC2 genes, respectively (Kim & Hong 2016). The incidence of NEN among patients with these syndromes varies considerably. Indeed, the incidence is very high in patients with MEN type 1 and is represented by isolated reports describing a small number of patients with TSC (Larson et al. 2012, Koc et al. 2017).

    Notably, epidemiological studies have demonstrated that non-syndromic individuals with an affected relative are at an increased risk of developing gastroenteropancreatic (GEP) NENs. In individuals with affected siblings, the relative risk of GEP NEN increases by 13.4-fold, and an increased risk (2.3-fold) is present even in third-degree relatives (Neklason et al. 2016). Collectively, these epidemiological studies suggest the existence of additional genetic determinants leading to the development of GEP NENs in non-syndromic patients.

    Here, we screened non-syndromic patients with GEP NEN for the presence of rare germline variants in genes previously associated with NEN-predisposing syndromes and searched for variants that could increase the risk of developing NENs without being associated with the corresponding syndromes.

    Ninety-three patients with any grade GEP NENs and with no clinical or molecular diagnosis of MEN type 1 or 2, von-Hippel–Lindau disease, neurofibromatosis syndrome or …

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    1. Endocr Relat Cancer 25 L1-L5
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