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Detecting & Quantifying Metallothionein Isoforms as Cancer & Metal Toxicity Biomarkers

Technology Benefits

Advantages:Simultaneously measure all human MT isoforms, with sensitivity to detect single amino acid differencesQuantify relative or absolute levels of all MT isoforms by Mass Spec, including post-translational modificationsUse for research, diagnosis/prognosis of cancers, and monitoring heavy metal exposure

Technology Application

Diagnostic/Prognosis of CancerMonitoring heavy metal exposure

Detailed Technology Description

Mass spectrometry is often used to analyze proteins in biological samples, but MT isoforms have proven challenging because they are small and not easily quantifiable by conventional proteomics strategies. Our technology enables absolute and relative quantification of each MT isoform in a sample using Mass Spec. As sensitive as RNA detection, our method has the advantages of measuring protein directly and distinguishing post-transcriptional variants. This allows the presence and amount of each isoform to be determined at a precision needed for cancer diagnostics and prognostics, and for metal exposure and toxicity monitoring purposes.

Supplementary Information

Patent Number: WO2013173756A8
Application Number: WO2013US41651A
Inventor: SHABB, John B. | MEHUS, Aaron | MUHONEN, Wallace | SENS, Donald A. | GARRETT, Scott
Priority Date: 18 May 2012
Priority Number: WO2013173756A8
Application Date: 17 May 2013
Publication Date: 20 Feb 2014
IPC Current: G01N003368
Assignee Applicant: University of North Dakota
Title: A METHOD FOR QUANTIFYING PROTEINS AND ISOFORMS THEREOF | MÉTHODE DE QUANTIFICATION DE PROTÉINES ET D'ISOFORMES DE CES PROTÉINES
Usefulness: A METHOD FOR QUANTIFYING PROTEINS AND ISOFORMS THEREOF | MÉTHODE DE QUANTIFICATION DE PROTÉINES ET D'ISOFORMES DE CES PROTÉINES
Summary: For quantifying an amount of a metallothionein isomer peptide in a test sample used for treating cancer (including breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, bladder cancer, ductal carcinoma, nasopharyngeal carcinoma, colorectal cancer, thyroid carcinoma, hepatocellular carcinoma, leukemia, lymphoma, melanoma, fibrosarcoma, neuroblastoma, autoimmune deficiency syndrome-associated Kaposi's sarcoma, adrenal cortex cancer, pheochromocytoma, cervical cancer, endometrial cancer, esophageal cancer, liver cancer, pancreatic cancer, prostate cancer, thymus cancer, chronic lymphocytic leukemia, Ewing's sarcoma, gestational trophoblastic tumor, hepatoblastoma, multiple myeloma, non-small cell lung cancer, retinoblastoma and bone cancer) or heavy metal poisoning; in kit as companion diagnostic for detection or monitoring of disease, for detecting and/or monitoring cancer, toxic exposure, heavy metal poisoning, or the development of metal toxicity induced by a platinum-based chemotherapy (claimed).
Novelty: Quantifying amount of metallothionein isomer peptide in test sample used for treating e.g. cancer involves mass spectroscopy, where the metallothionein isomer peptide is an N-terminal peptide from cleavage of metallothionein protein isomer

Industry

Disease Diagnostic/Treatment

Sub Category

Cancer/Tumor

*Abstract

Metallothionein (MT) proteins bind with high affinity to heavy metals. The twelve MT isoforms also appear to be differentially expressed in patterns that may be indicative of specific cancer and cancer subtypes (including subtypes of breast, bladder and kidney cancers), and exposure to specific metals. Precise identification and quantification of MT isoforms in a tissue sample could be used in cancer and heavy metal exposure diagnosis and prognosis. However, antibody-based methods have not provided reliable differentiation due to high sequence conservation among MT isoforms. RNA-based analysis doesnΓÇÖt measure protein abundance or reflect post-translational modifications. The technology described here overcomes these limitations, and enables development of a kit to detect and quantify any MT isoforms present in a tissue sample.

*Principal Investigator

Name: John Shabb, Associate Professor

Department: Basic Sciences

Country/Region

USA