Germline and Somatic Mutations in the Tyrosine Kinase Domain of the MET Proto-Oncogene in Papillary Renal Carcinomas

Schmidt, Laura S.; Duh, Fuh Mei; Chen, F.; Kishida, Takeshi; Choyke, Peter L.; Scherer, Stephen W.; Zhuang, Zhengping; Lubensky, Irina A.; Dean, Michael; Allikmets, Rando; Chidambaram, Abirami; Bergerheim, U. R.; Feltis, J.T.; Casadevall, Carme; Zamarrón, A.; Bernués, Marta; Richard, Stephanie A; Lips, C. J. M.; Walther, McClellan M.; Tsui, Lap Chee; Geil, L.; Orcutt, M.L.; Stackhouse, Thomas; Lipan, J.; Slife, L.; Brauch, Hiltrud; Decker, Jochen; Niehans, Gloria A.; Hughson, Michael D.; Moch, Holger; Störkel, Stefan; Lerman, M. I.; Linehan, W. Marston; Zbar, B.

doi:10.1016/s0022-5347(01)63909-0

Cited by 247 publications

(322 citation statements)

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“…In addition to VHL, SDH 90,91 , FH 92 and TMEM127 (REFS 93,94), genes can also be mutated in renal carcinomas either with or without co-occurrence of PPGL. The MET gene, previously known to cause hereditary papillary renal cancer 95 , was also found to be mutated in PPGLs 14,96 . Finally, somatic mutations in chromatin remodelling genes are recurrently detected in renal carcinomas and PPGLs 14,[96][97][98] .…”

Section: Discussionmentioning

confidence: 96%

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

et al. 2016

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Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. This Consensus Statement, formulated by a study group comprised of experts in the field, proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. In brief, the study group recommends target gene panels for screening of germ line DNA, technical adaptations to address different modes of disease transmission, orthogonal validation of NGS findings, standardized classification of variant pathogenicity and uniform reporting of the findings. The use of supplementary assays, to aid in the interpretation of the results, and sequencing of tumour DNA, for identification of somatic mutations, is encouraged. In addition, the study group launches an initiative to develop a gene-centric curated database of PPGL variants, with annual re-evaluation of variants of unknown significance by an expert group for purposes of reclassification and clinical guidance.

Funding Agencies|Cancer Prevention and Research Institute of Texas (CPRIT) [RP101202, RP57154]; Department of Defense [CDMRP W81XWH-12-1-0508]; Voelcker Fund; National Institutes of Health (NIH)s National Center for Research Resources; National Center for Advancing Translational Sciences [8UL1TR000149]; INSERM; French National Cancer Institute (INCA); Direction Generale de lOffre de Soins (DGOS); INCA [INCA-DGOS_8663]; European Union [633983]; Brazilian National Council for Scientific and Technological Development (CNPq); Cancer Research for PErsonalized Medicine (CARPEM); ERC Advanced Researcher Award

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Section: Discussionmentioning

confidence: 96%

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

et al. 2016

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“…In papillary RCC, frequently detected genetic alterations include trisomy of chromosomes 3q, 7, 8, 12, 16, 17 and 20, and loss of the Y chromosome (Kovacs et al, 1991;Jiang et al, 1998). Although the MET proto-oncogene (7q31) is implicated in the pathogenesis of papillary RCC, only a small percentage of the cases of the sporadic papillary RCC have MET mutations (Schmidt et al, 1997). This suggests that the tumorigenic process may require aberrant alterations of additional genes.…”

Section: Discussionmentioning

confidence: 99%

“…Wilms tumor, also known as nephroblastoma, mostly affects children (Rivera and Haber, 2005). The majority of renal tumors occur sporadically, but a minority (B2%) of cases are associated with hereditary renal cancer diseases, such as the von Hippel-Lindau (VHL) syndrome (Latif et al, 1993), the hereditary papillary renal cancer (HPRC) syndrome (Schmidt et al, 1997), the hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome (Tomlinson et al, 2002) and the Birt-Hogg-Dube´(BHD) syndrome (Nickerson et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, inactivation of VHL through methylation or loss of heterozygosity (LOH) occurs frequently in clear cell RCC (Herman et al, 1994;Moch et al, 1998;Brauch et al, 2000). The MET, FH and BHD genes have been identified to cause HPRC syndrome, HLRCC syndrome and BHD syndrome, respectively (Schmidt et al, 1997;Nickerson et al, 2002;Tomlinson et al, 2002) and their somatic mutations were also found in some sporadic counterparts of their hereditary tumor subtypes (Schmidt et al, 1999;Kiuru et al, 2002;Khoo et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

et al. 2006

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Inactivation of the HRPT2 gene encoding parafibromin was recently linked to the familial hyperparathyroidismjaw tumor syndrome. Patients with this syndrome carry an increased risk of parathyroid and renal tumors. To determine the relevance of HRPT2 for sporadic renal tumors, clear cell, papillary and chromophobe renal cell carcinomas as well as oncocytomas and Wilms tumors were analysed for HRPT2 gene alterations. Loss of heterozygosity (LOH) of HRPT2 was found in seven of 56 (12.5%) clear cell, three of 14 (21%) papillary, six of 10 (60%) chromophobe renal cell carcinomas, three of eight (38%) oncocytomas and four of 10 (40%) Wilms tumors. In addition, two novel HRPT2 point mutations, causing K34Q and R292K changes in parafibromin, were detected in one clear cell carcinoma and one Wilms tumor, respectively. These tumors displayed LOH of the remaining wild-type allele, but interestingly no von HippelLindau (VHL) mutation. Functional analysis revealed that the K34Q mutant species of parafibromin is, unlike wild-type protein, defective in suppressing cyclin D1 expression in vivo. Taken together, these results suggest that renal cancer-associated mutations in parafibromin occur in the absence of VHL mutation, which in turn may contribute to constitutively elevated cyclin D1 expression and abnormal cell proliferation.

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“…However, recent data suggest that this is unlikely to be the case. In a limited number of tumour cells featuring genetic lesions of MET -caused by gene amplification and, possibly, point mutations 23,140,141 -receptor hyperactivation is inherent in the cancer's natural history and is required to maintain the transformed phenotype: these cells are dependent on the persistent activity of MET for their relentless proliferation (a situation known as 'oncogene addiction') 142,143 . In this scenario, MET blockade affects a limited subset of MET downstream signals: many of the pathways controlling MET-driven responses -including STATs, JNK, p38 and NF-κB -remain active or exhibit scant responses, and only a restricted complement of Ras and PI3K transducers and transcriptional effectors is neutralized 144,145,146 .…”

Section: Met Signalling In Development and Diseasementioning

confidence: 99%

MET signalling: principles and functions in development, organ regeneration and cancer

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,083

1,076

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The MET tyrosine kinase receptor (also known as the HGF receptor) promotes tissue remodelling, which underlies developmental morphogenesis, wound repair, organ homeostasis and cancer metastasis, by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations. The versatility of MET-mediated biological responses is sustained by qualitative and quantitative signal modulation. Qualitative mechanisms include the engagement of dedicated signal transducers and the subcellular compartmentalization of MET signalling pathways, whereas quantitative regulation involves MET partnering with adaptor amplifiers or being degraded through the shedding of its extracellular domain or through intracellular ubiquitylation. Controlled activation of MET signalling can be exploited in regenerative medicine, whereas MET inhibition might slow down tumour progression.Throughout embryogenesis, cells bud off from developing tissues and move outwards to shape and pattern the complex architecture of prospective organs 1 . A similar process occurs in adult life during wound healing and tissue repair, when lingering cells migrate into injury sites to recreate the pre-existing structures 2 . The acquisition of cell motility is necessary, but not sufficient, for this event. Cells that detach from their neighbours must elude anoikis, a form of apoptotic cell death that occurs when cells lose adhesion with the extracellular matrix 3 . Moreover, migratory cells undergo extensive mitotic divisions to produce 'founder populations', which settle in newly forming organs during development or colonize worn tissues during repair 4,5 . The normal phases of embryogenesis and organ regeneration strongly resemble the pathological process of tumour invasiveness: similarly to cells at the wound edge, cells at the tumour's leading front disrupt intercellular contacts and infiltrate the adjacent surroundings, where they resist anoikis and grow before lodging in the blood vessels for systemic dissemination 6 . This resemblance is not simply a biological correlate, it has a common mechanistic basis: cancer cells resurrect the latent schemes of cellular reorganization, which are usually confined to embryonic development and damaged adult organs, and leverage them to become competent for metastasization 7 . The activities -motility, survival and proliferation -that occur in developing, injured and neoplastic tissues embody a biological programme that is defined as 'invasive growth' 8 . This is triggered by extracellular stimuli that regulate the activity of several transcription factors that, in turn, modulate the expression of a number of proteins, ranging from cytoskeletal and cell-cell junctional components to cell cycle regulators and anti-apoptotic effectors 9, 10 . One major environmental inducer of invasive growth is hepatocyte growth factor (HGF, also known as scatter factor), the ligand for the MET tyrosine kinase receptor (also known as the HGF receptor) 11,12,13,14,15,16,17,18,19,20 (Box 1). ...

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Germline and Somatic Mutations in the Tyrosine Kinase Domain of the MET Proto-Oncogene in Papillary Renal Carcinomas

Cited by 247 publications

References 0 publications

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

MET signalling: principles and functions in development, organ regeneration and cancer

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