MET mutations are associated with aggressive and radioresistant brain metastatic non-small-cell lung cancer: Table 1.

Stella, Giulia Maria; Senetta, Rebecca; Inghilleri, Simona; Cantogno, Ludovica Verdun di; Mantovani, Cristina; Piloni, Davide; Scudeller, Luigia; Meloni, Federica; Papotti, Mauro; Ricardi, Umberto; Cassoni, Paola

doi:10.1093/neuonc/nov325

Cited by 15 publications

(9 citation statements)

References 9 publications

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“…Thus, our data strongly suggest that the non-catalytic SEMA domain is involved in neoplastic invasiveness, although no clear mechanistic explanation is given by only biological characterization of SEMA mutants. Notably, we further demonstrated that the occurrence of SEMA mutations is associated with aggressive and radioresistant brain metastasis from known primary (lung) ( Stella et al, 2016a , Stella et al, 2016b ) thus confirming the tumorigenic potential of SEMA-mutated cells. Those findings allowed us to hypothesize that changes affecting the SEMA domain coding sequence may be reflected in structural alteration of the extracellular portion of the MET receptor.…”

Section: The Met-driven Invasive Growth Program In Metastasis and Cupsupporting

confidence: 71%

MET Activation and Physical Dynamics of the Metastatic Process: The Paradigm of Cancers of Unknown Primary Origin

et al. 2017

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The molecular and cellular mechanisms which drive metastatic spread are the topic of constant debate and scientific research due to the potential implications for cancer patients' prognosis. In addition to genetics and environmental factors, mechanics of single cells and physical interaction with the surrounding environment play relevant role in defining invasive phenotype. Reconstructing the physical properties of metastatic clones may help to clarify still open issues in disease progression as well as to lead to new diagnostic and therapeutic approaches. In this perspective cancer of unknown primary origin (CUP) identify the ideal model to study physical interactions and forces involved in the metastatic process. We have previously demonstrated that MET oncogene is mutated with unexpected high frequency in CUPs. We here analyze and discuss how the MET activation by somatic mutation may affect physical properties in giving rise to such a highly malignant syndrome, as that defined by CUP.

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Section: The Met-driven Invasive Growth Program In Metastasis and Cupsupporting

confidence: 71%

MET Activation and Physical Dynamics of the Metastatic Process: The Paradigm of Cancers of Unknown Primary Origin

et al. 2017

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“…MET-driven invasive growth is aberrantly activated in cancer, mainly as a late event, leading to distant dissemination and malignant progression. More recent studies have reported that MET amplified cancer clones are selected under therapeutic pressure in a context of molecularly heterogeneous lesions exposed to targeted therapies or radiotherapy [ 8 , 122 – 125 ]. In CSC, both the occurrence of genetic lesions (as amplification) and physiological expression of MET can contribute to tumorigenesis and therapeutic resistance, by sustaining the invasive growth phenotype.…”

Section: Introductionmentioning

confidence: 99%

Ockham’s razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer

et al. 2016

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Background: Idiopathic pulmonary fibrosis (IPF) identifies a specific lung disorder characterized by chronic, progressive fibrosing interstitial pneumonia of unknown etiology, which lacks effective treatment. According to the current pathogenic perspective, the aberrant proliferative events in IPF resemble those occurring during malignant transformation. Main body:Receptor tyrosine kinases (RTK) are known to be key players in cancer onset and progression. It has been demonstrated that RTK expression is sometimes also altered and even druggable in IPF. One example of an RTK-the MET proto-oncogene-is a key regulator of invasive growth. This physiological genetic program supports embryonic development and post-natal organ regeneration, as well as cooperating in the evolution of cancer metastasis when aberrantly activated. Growing evidence sustains that MET activation may collaborate in maintaining tissue plasticity and the regenerative potential that characterizes IPF. Conclusion:The present work aims to elucidate-by applying the logic of simplicity-the bio-molecular mechanisms involved in MET activation in IPF. This clarification is crucial to accurately design MET blockade strategies within a fully personalized approach to IPF.

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“…Figure S2), 93 of which affected Sema domain‐encoding exons. Mutations involving this domain have been described in cancers of unknown primary origin (Stella et al., ) and radioresistant brain metastases from non‐small‐cell lung cancers (Stella et al., ). One Sema‐domain mutant in the TCGA data set (found in an adenoid cystic carcinoma) was a missense variation (p.Arg417Gly) involving the same amino acid position as the variant found in our kindred.…”

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confidence: 99%

Whole exome sequencing identifies a germline MET mutation in two siblings with hereditary wild-type RET medullary thyroid cancer

et al. 2017

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Whole exome sequencing (WES) was used to investigate two Italian siblings with wild-type RET genotype, who developed medullary thyroid cancers (MTCs) and, later, primary prostate and breast cancers, respectively. The proband's MTC harbored a p.Met918Thr RET mutation; his sister's MTC was RET/RAS wild-type. Both siblings had a germline mutation (p.Arg417Gln) in the extracellular Sema domain of the proto-oncogene MET. Experiments involving ectopic expression of MET p.Arg417Gln in MET-negative T47D breast cancer cells documented the mutant receptor's functionality and its ability to enhance cell migration and invasion. Our findings highlight a possible link between MET germline mutations and MTCs and suggest that MET p. Arg417Gln may promote an invasive malignant phenotype. The possibility that MTC can be driven/co-driven by a MET mutation has potential management implications, since the tyrosine-kinase inhibitor cabozantinib-approved for treating advanced MTCs-is a specific MET inhibitor.

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MET mutations are associated with aggressive and radioresistant brain metastatic non-small-cell lung cancer: Table 1.

Cited by 15 publications

References 9 publications

MET Activation and Physical Dynamics of the Metastatic Process: The Paradigm of Cancers of Unknown Primary Origin

MET Activation and Physical Dynamics of the Metastatic Process: The Paradigm of Cancers of Unknown Primary Origin

Ockham’s razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer

Whole exome sequencing identifies a germline MET mutation in two siblings with hereditary wild-type RET medullary thyroid cancer

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