Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

UDP-galactose:N-acetylglucosamine galactosyltransferase (GT) is a membrane-bound enzyme active in the biosynthesis of the carbohydrate moiety of glycoproteins and glycolipids. A soluble form of GT, present in human serum, has recently been found to be elevated in the presence of various neoplasms. In this study, GT levels were measured in randomized serum samples obtained from normal controls (group I, n = 49), patients with benign breast disease (group II, n = 46), disease controls (group III, n = 50), patients with primary breast carcinoma (group IV, n = 53), and untreated metastatic breast cancer (group V, n = 23). Although substantial serum GT elevations were observed in individual control patients with active inflammatory or metabolic diseases, the mean GT levels were significantly higher in the groups with breast carcinoma (P < 0.001, 0.001, 0.02; P < 0.001, 0.001, 0.001 for groups IV and V vs groups, 1, II, and III, respectively). Furthermore, when serum GT levels were correlated with the properative clinical stage of breast cancer, significant elevations were found in 14.3% (3/21) of stage I, 66.7% (8/12) of stage II, 78.6% (11/14) of stage III, and 96.5% (28/29) of stage IV patients. These data indicate that serum GT levels are elevated in the presence of breast carcinoma and that the enzyme elevations correlate positively with the clinical stage of disease. Serum GT may be potentially useful in the detection of recurrent breast carcinoma and as a marker of tumor response to therapy for advanced disease.
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PMID:Serum UDP-galactosyl transferase as a potential biomarker for breast carcinoma. 677 60

Nearly all breast cancer deaths result from metastatic disease. Despite this, the genomic events that drive metastatic recurrence are poorly understood. We performed whole-exome and shallow whole-genome sequencing to identify genes and pathways preferentially mutated or copy-number altered in metastases compared with the paired primary tumors from which they arose. Seven genes were preferentially mutated in metastases - MYLK, PEAK1, SLC2A4RG, EVC2, XIRP2, PALB2, and ESR1 - 5 of which are not significantly mutated in any type of human primary cancer. Four regions were preferentially copy-number altered: loss of STK11 and CDKN2A/B, as well as gain of PTK6 and the membrane-bound progesterone receptor, PAQR8. PAQR8 gain was mutually exclusive with mutations in the nuclear estrogen and progesterone receptors, suggesting a role in treatment resistance. Several pathways were preferentially mutated or altered in metastases, including mTOR, CDK/RB, cAMP/PKA, WNT, HKMT, and focal adhesion. Immunohistochemical analyses revealed that metastases preferentially inactivate pRB, upregulate the mTORC1 and WNT signaling pathways, and exhibit nuclear localization of activated PKA. Our findings identify multiple therapeutic targets in metastatic recurrence that are not significantly mutated in primary cancers, implicate membrane progesterone signaling and nuclear PKA in metastatic recurrence, and provide genomic bases for the efficacy of mTORC1, CDK4/6, and PARP inhibitors in metastatic breast cancer.
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PMID:Genomic landscape of metastatic breast cancer identifies preferentially dysregulated pathways and targets. 3265 79