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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 …
JK and KR contributed equally.
Contributors JK and KR performed morphological and immunohistochemical studies, analysed the data and wrote the manuscript. TH and PL-K performed morphological studies. EP and UW contributed cases and clinical data and revised the manuscript. CT designed the research, performed morphological studies and revised the manuscript. All authors read and approved the final version of the manuscript.
Competing interests None declared.
Ethics approval Ethics Committee Luebeck.
Provenance and peer review Not commissioned; externally peer reviewed.