DNA methylation biomarkers and their utility for solid cancer diagnostics
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Karen A. Heichman
Dr. Karen A. Heichman is the Vice President of Technology Development and in-licensing in the area of oncology at ARUP Laboratories, Inc., a national reference laboratory in Salt Lake City, which is an enterprise of the University of Utah. She is also an Assistant Professor at the University of Utah School of Medicine. Her role at ARUP involves both developing and managing scientific and business collaborations, with the goal of identifying and implementing new oncology tests and technologies for use in the clinical laboratory setting. Dr. Heichman holds an undergraduate degree in genetics from the University of California at Berkeley and a PhD in biological chemistry from the UCLA School of Medicine, and trained as a postdoctoral fellow in the field of cycle control at the Fred Hutchinson Cancer Research Center in Seattle. Dr. Heichman has over 25 years of scientific experience in both corporate and academic institutions.
and
Jorja D. Warren
Jorja D. Warren is a technical specialist at ARUP Laboratories, Inc. She has worked in laboratory research for over 11 years, mainly in the area of molecular biology and diagnostics. She holds an undergraduate degree from Arizona State University in the field of biology. Ms Warren spent several years at Myriad Genetics in Salt Lake City before joining the New Technology Group at ARUP Laboratories in 2009. She has focused primarily on epigenetics since coming to ARUP and is credited with developing and validating a sensitive Septin 9 blood-based colorectal cancer screening test that is currently offered clinically.
Abstract
Cellular DNA undergoes profound changes in methylation during cancer development, with hypermethylation occurring in specific gene promoters, amidst a backdrop of generalized hypomethylation. DNA methylation in cancer often causes the silencing of tumor suppressors and other genes important for cellular growth, regulation and differentiation. Over the past two decades, there have been thousands of publications describing the methylation status of hundreds of genes in cancer, with numerous associations with clinical states, disease outcomes and therapeutic responses being reported. New methods for DNA methylation fingerprinting have emerged, allowing for the exponential growth of “epigenomic” information. Despite this wealth of data, only a handful of methylated genes are utilized as cancer biomarkers in the clinical laboratory. A literature review centered on DNA methylation in six solid cancers was performed, including colorectal, pancreatic, prostate, bladder, breast and ovarian. Commonly methylated genes in the six cancer types were identified and catalogued, and could serve in the future as tissue-based biomarkers or as part of cancer-specific panels. Perhaps more importantly, this endeavor has also focused on methylated genes that appear to be unique to particular cancers. These genes may be more versatile for clinical use, with blood or urine-based cancer screening becoming a reality.
About the authors
Dr. Karen A. Heichman is the Vice President of Technology Development and in-licensing in the area of oncology at ARUP Laboratories, Inc., a national reference laboratory in Salt Lake City, which is an enterprise of the University of Utah. She is also an Assistant Professor at the University of Utah School of Medicine. Her role at ARUP involves both developing and managing scientific and business collaborations, with the goal of identifying and implementing new oncology tests and technologies for use in the clinical laboratory setting. Dr. Heichman holds an undergraduate degree in genetics from the University of California at Berkeley and a PhD in biological chemistry from the UCLA School of Medicine, and trained as a postdoctoral fellow in the field of cycle control at the Fred Hutchinson Cancer Research Center in Seattle. Dr. Heichman has over 25 years of scientific experience in both corporate and academic institutions.
Jorja D. Warren is a technical specialist at ARUP Laboratories, Inc. She has worked in laboratory research for over 11 years, mainly in the area of molecular biology and diagnostics. She holds an undergraduate degree from Arizona State University in the field of biology. Ms Warren spent several years at Myriad Genetics in Salt Lake City before joining the New Technology Group at ARUP Laboratories in 2009. She has focused primarily on epigenetics since coming to ARUP and is credited with developing and validating a sensitive Septin 9 blood-based colorectal cancer screening test that is currently offered clinically.
©2012 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Masthead
- Masthead
- Editorials
- Cancer epigenomics: moving slowly, but at a steady pace from laboratory bench to clinical practice
- Laboratory networking and sample quality: a still relevant issue for patient safety
- Reviews
- DNA methylation biomarkers and their utility for solid cancer diagnostics
- DNA methylation biomarkers in biological fluids for early detection of respiratory tract cancer
- Global DNA hypomethylation in cancer: review of validated methods and clinical significance
- Genetics and Molecular Diagnostics
- δ0-Thalassemia in cis of βKnossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients
- Genetic-based reference values for angiotensin-converting enzyme (ACE) according to I/D polymorphism in a Spanish population sample
- General Clinical Chemistry and Laboratory Medicine
- Effects of sample transportation on commonly requested laboratory tests
- Long-term (in)stability of folate and vitamin B12 in human serum
- Information comparison of the effects of drugs on laboratory tests in drug labels and Young’s book
- First evaluation of Capillarys 2 Flex Piercing® (Sebia) as a new analyzer for HbA1c assay by capillary electrophoresis
- Antioxidant and oligonutrient status, distribution of amino acids, muscle damage, inflammation, and evaluation of renal function in elite rugby players
- Validation of the body fluid module on the new Sysmex XN-1000 for counting blood cells in cerebrospinal fluid and other body fluids
- Measuring Rivaroxaban in a clinical laboratory setting, using common coagulation assays, Xa inhibition and thrombin generation
- Cancer Diagnostics
- Increased concentrations of growth factors and activation of the EGFR system in breast cancer
- Infectious Diseases
- Incidence and significance of elevated lactate in the identification of critically ill patients
- Cardiovascular Diseases
- Lipoprotein-associated phospholipase A2 is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis
- Diabetes
- Serum cystatin C as a marker for early detection of chronic kidney disease and grade 2 nephropathy in Japanese patients with type 2 diabetes
- Letters to the Editor
- Establishing professional phlebotomist group for quality control of the preanalytic variables of clinical laboratory
- Application of quality specification based on biological variation in planning quality control strategy
- Analytical and clinical evaluation of a new immunoassay for therapeutic drug monitoring of infliximab and adalimumab
- Comparison of relationships between FT4 and log TSH in Access DXI 800 Unicel, Modular E170 and ADVIA Centaur XP Analyzer
- Assay-specific pitfalls of catecholamine HPLC assays
- Evaluation of automated nucleated red blood cells counting on Sysmex XE5000 and Siemens ADVIA 2120
- Evaluation of the immature myeloid information (IMI) by Sysmex XE 2100® hematology analyzer in the identification of blasts of myeloid lineage
- Congress Abstracts
- Congress of Laboratory Medicine and Clinical Chemistry / 4th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC)
- Abstracts of the 2012 Convocation of Experts on Laboratory Quality / Embracing the Need of Continued Vigilance to Assure Quality Outcomes in the Modern Laboratory
Articles in the same Issue
- Masthead
- Masthead
- Editorials
- Cancer epigenomics: moving slowly, but at a steady pace from laboratory bench to clinical practice
- Laboratory networking and sample quality: a still relevant issue for patient safety
- Reviews
- DNA methylation biomarkers and their utility for solid cancer diagnostics
- DNA methylation biomarkers in biological fluids for early detection of respiratory tract cancer
- Global DNA hypomethylation in cancer: review of validated methods and clinical significance
- Genetics and Molecular Diagnostics
- δ0-Thalassemia in cis of βKnossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients
- Genetic-based reference values for angiotensin-converting enzyme (ACE) according to I/D polymorphism in a Spanish population sample
- General Clinical Chemistry and Laboratory Medicine
- Effects of sample transportation on commonly requested laboratory tests
- Long-term (in)stability of folate and vitamin B12 in human serum
- Information comparison of the effects of drugs on laboratory tests in drug labels and Young’s book
- First evaluation of Capillarys 2 Flex Piercing® (Sebia) as a new analyzer for HbA1c assay by capillary electrophoresis
- Antioxidant and oligonutrient status, distribution of amino acids, muscle damage, inflammation, and evaluation of renal function in elite rugby players
- Validation of the body fluid module on the new Sysmex XN-1000 for counting blood cells in cerebrospinal fluid and other body fluids
- Measuring Rivaroxaban in a clinical laboratory setting, using common coagulation assays, Xa inhibition and thrombin generation
- Cancer Diagnostics
- Increased concentrations of growth factors and activation of the EGFR system in breast cancer
- Infectious Diseases
- Incidence and significance of elevated lactate in the identification of critically ill patients
- Cardiovascular Diseases
- Lipoprotein-associated phospholipase A2 is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis
- Diabetes
- Serum cystatin C as a marker for early detection of chronic kidney disease and grade 2 nephropathy in Japanese patients with type 2 diabetes
- Letters to the Editor
- Establishing professional phlebotomist group for quality control of the preanalytic variables of clinical laboratory
- Application of quality specification based on biological variation in planning quality control strategy
- Analytical and clinical evaluation of a new immunoassay for therapeutic drug monitoring of infliximab and adalimumab
- Comparison of relationships between FT4 and log TSH in Access DXI 800 Unicel, Modular E170 and ADVIA Centaur XP Analyzer
- Assay-specific pitfalls of catecholamine HPLC assays
- Evaluation of automated nucleated red blood cells counting on Sysmex XE5000 and Siemens ADVIA 2120
- Evaluation of the immature myeloid information (IMI) by Sysmex XE 2100® hematology analyzer in the identification of blasts of myeloid lineage
- Congress Abstracts
- Congress of Laboratory Medicine and Clinical Chemistry / 4th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC)
- Abstracts of the 2012 Convocation of Experts on Laboratory Quality / Embracing the Need of Continued Vigilance to Assure Quality Outcomes in the Modern Laboratory
