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Prognostic implications of RASAL1 expression in oesophagogastric adenocarcinoma
  1. Juliana Knief1,
  2. Katharina Reddemann1,
  3. Pamela Lazar-Karsten1,
  4. Tobias Herhahn1,
  5. Ekaterina Petrova2,
  6. Ulrich Wellner2,
  7. Christoph Thorns1
  1. 1Department of Pathology, Section of Hematopathology and endocrine Pathology, University Hospital of Schleswig-Holstein, Luebeck, Germany
  2. 2Department of Surgery, University Hospital of Schleswig-Holstein, Luebeck, Germany
  1. Correspondence to : Dr Juliana Knief, Section of Hematopathology and Endocrine Pathology, Department of Pathology, University Hospital of Schleswig-Holstein, Campus Luebeck, Luebeck 23538, Germany; Juliana.Knief{at}uksh.de

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Activation of RAS signalling through the RAS-RAF-MEK-ERK cascade is a well-established event in various human cancers, leading to increased cell proliferation, inhibition of apoptosis and immortalisation of tumour cells.1 ,2 Recently, RASAL1 (RAS protein activator like 1), a RAS GTPase-activating protein, which catalyses the inactivation of RAS, has been shown to act as a tumour suppressor in thyroid carcinoma, providing a potential alternative genetic background for tumours not harbouring ‘classical’ mutations in RAS or BRAF genes.3 RASAL1 belongs to the so-called ‘RAS superfamily GTPases’ and has been reported to harbour somatic mutations exclusively in the RAS GTPase-activating domain, leading to impairment of suppression in the RAS-RAF-MEK-ERK cascade.4 Silencing of RASAL1 leads to increased tumorigenesis via uncontrolled mobilisation of GTPases,4 which is most commonly mediated through hypermethylation or inactivating (missense) mutations.5 ,6

In recent studies, it could be demonstrated that expression of RASAL1 was significantly reduced and RASAL1 was commonly silenced in thyroid cancer cell lines compared with non-neoplastic counterparts.7 Reduced expression of RASAL1 as well as associations with less favourable clinical factors (ie, tumour size, presence of lymph node metastases, differentiation grade and depth of invasion) has also been reported in gastric and colorectal adenocarcinomas.1 ,8 As of yet, the prognostic implications of RASAL1 are still unclear, especially concerning gastrointestinal tumours. Therefore, we sought …

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