Cancer, neurological disorders

Hypermethioninemia (MET)

Hypermethioninemia (MET) arises from abnormal amounts of methionine, an amino acid, in the blood. MET can be affiliated with the liver, brain (overall), and cortex of the brain.
 

Hepatocellular carcinomas (HCC); Renal cell carcinomas, papillary, 1, Familial and somatic; Papillary renal carcinomas; Hepatocellular carcinomas, somatic; Renal cell carcinomas; Papillary carcinomas; Malignant mesothelioma; lung cancer; Salivary gland cancer; Hepatocellular carcinomas, Childhood; Papillary renal cell carcinomas (RCCP); Hepatoblastoma, somatic; Colorectal cancer; Osteosarcoma; Cholangiocarcinomas (CCA); Chordoma; Spinal Chordoma; Alveolar Soft Part Sarcoma (ASPS); Inflammatory Breast carcinomas (IBC); Inflammatory Breast carcinomas; Acral lentiginous melanomas (ALM); Gastric cardia adenocarcinomas; Tall cell variant papillary carcinomas

MET is a known oncoprotein (OP). Cancer-related mutations in human tumours point to a gain of function of the protein kinase. The active form of the protein kinase normally acts to promote tumour cell proliferation. Hepatocellular carcinoma (HCC) occurs with higher risk in those that have chronic HCV (hepatitis C virus) or HBV (hepatitis B virus) infection, or aflatoxin exposure in diet, or alcohol-induced cirrhosis, or another form of cirrhosis. HCC is a tumour of the epithelial liver cells. Renal Cell Carcinoma is a kidney carcinoma arising from the proximal renal tube. Malignant Mesothelioma is a carcinoma of the mesothelial tissue (a membrane encapsulating various body cavities like the peritoneum around the abdomen) which can affect breast, lung, and testis tissues. Salivary Gland Cancer is a rare head and neck cancer which may be asymptomatic. Lumps can occur in the ear, cheek, jaw, or lip. Papillary Renal Cell Carcinoma (RCCP) is a rare kidney cancer and can affect the kidney, thyroid, or brain. Osteosarcoma accounts for the most bone marrow cancers in youth, but can also be associated with lung and breast tissue. The rare liver cancer Cholangiocarcinoma (CCA) arises from transformed epithelial cells and may include symptoms such as abnormally dark urine, and itching alongside tumour development. Chordoma is a cancer which will develop from the notochord, which is essential for spine development, but typically will not be diagnosed until later in life. Chordoma is characterized by invading surrounding bone, not metastasizing throughout the body, and leading to headaches, and double vision. Alveolar Soft Part Sarcoma (ASPS) is related to the sarcoma and granular cell tumour disorders. ASPS is a soft-tissue cancer of unknown origin and which can affect the tongue, cervix, or breast. A rare breast cancer, Inflammatory Breast Carcinoma (IBC), is characterized by the formation of a blockage in the lymph nodes, leading to generally inflamed tissue. The rare skin melanoma Acral Lentiginous Melanoma (ALM) can arise from melanocytes, typically on the soles of the feet, palms of the hands, under a nail, or in oral mucosa. ALM does not appear to have a link to sunlight for causing cancer.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Barrett's esophagus epithelial metaplasia (%CFC= +98, p<(0.0003); Brain oligodendrogliomas (%CFC= +50, p<0.044); Breast epithelial carcinomas (%CFC= -62, p<0.004); Clear cell renal cell carcinomas (cRCC) (%CFC= +95, p<0.091); Colon mucosal cell adenomas (%CFC= +234, p<0.0001); Malignant pleural mesotheliomas (MPM) tumours (%CFC= +143, p<0.001); Oral squamous cell carcinomas (OSCC) (%CFC= +51, p<0.0006); Ovary adenocarcinomas (%CFC= -78, p<0.003); Papillary thyroid carcinomas (PTC) (%CFC= +192, p<0.051); Pituitary adenomas (ACTH-secreting) (%CFC= -53, p<0.08); Prostate cancer - primary (%CFC= +93, p<0.0001); Skin melanomas - malignant (%CFC= +120, p<0.0001); and Uterine leiomyomas from fibroids (%CFC= -47, p<0.002). The COSMIC website notes an up-regulated expression score for MET in diverse human cancers of 515, which is 1.1-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 4 for this protein kinase in human cancers was 0.1-fold of the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.11 % in 36569 diverse cancer specimens. This rate is a modest 1.48-fold higher than the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.42 % in 1611 large intestine cancers tested; 0.26 % in 1678 upper aerodigestive tract cancers tested; 0.24 % in 1749 skin cancers tested; 0.22 % in 1744 kidney cancers tested; 0.19 % in 749 endometrium cancers tested; 0.17 % in 565 urinary tract cancers tested; 0.14 % in 4365 lung cancers tested; 0.13 % in 954 stomach cancers tested; 0.11 % in 1481 liver cancers tested; 0.09 % in 1332 ovary cancers tested; 0.05 % in 3043 haematopoietic and lymphoid cancers tested; 0.05 % in 2134 central nervous system cancers tested.

Most frequent mutations with the number of reports indicated in brackets: Y1253D (47); T1010I (31); M1268T (11); Y1248C (9); R988C (6).

In human tumours, the muations are particularly prevalent in 3 regions: amino acid residues 369-375; 982-1010; and 1246-1270.