Table 3.

Implications of c-Met Juxtamembrane Domain Mutations

Mutation	Tumor Type	Molecular Sequelae	Ref.
R988C & T1010I	SCLC	Transfection with mutant form resulted in increased paxicillin tyrosine Y31 phosphorylation, motility and tumorigenicity in vitro	[16]
G966S	n/a	Predisposition to cancer in Rottweiler dogs carrying this germline mutation; mutation rate 74%	[31]
T1010I	Murine	Increased tumorigenicity of mutant transfected NIH3T3 cells when injected in athymic nude mice	[32]
R968C	Murine	SWR/J mice, importance in lung tumorigenesis	[34]
R988C & T1010I	SCLC	Increased levels of reactive oxygen (ROS) formation	[35]
P991S	Gastric	Increased persistent response to HGF stimulation when expressed in fibroblasts	[33]
R988C & T1010I	MCF-7 cells	No effect on c-MET phosphorylation upon treatment with tyrosine kinase inhibitors BMS777067 and SU11274 (unstimulated condition)	current study
R988C & T1010I	Various*	No evidence of increased phosphorylation or transformative capacity	[21]
Splice mutation	NSCLC	Somatic intronic mutation causing a deletion of juxtamembrane domain resulting in loss of Cbl-E3-ligase binding resulting in decreased ubiquitination, delayed downregulation and enhanced c-Met activation	[19]
Y1001	Epithelial cells (MDCK)	Y1001 mutation was shown to produce constitutively mobile, fibroblastoid cells	[36]
R988C & T1010I	Healthy individuals	Autism association study. Germline mutation found in 1.8% of autistic individuals and in 0.6% of healthy controls (not significant)	[32]

Notes:

^*CLL, AML, CMML, colorectal, endometrial, thyroid, melanoma, healthy control.