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  1. University of Arkansas for Medical Sciences
  2. Winthrop P. Rockefeller Cancer Institute
  3. UAMS Myeloma Center
  4. Research
  5. Advanced Diagnostics for Advancing the Cure

Advanced Diagnostics for Advancing the Cure

Like other cancers, myeloma is characterized by genetic abnormalities, or mutations, that result from damage to normal cells.

In particular, the biologic mechanisms that control normal cell growth are affected. This wreaks havoc with the function of the cells through altered patterns of gene activity, known as gene expression.

The unique characteristics of each individual’s genetic make-up and the genetic changes that give rise to cancer result in a truly unique profile of behavior for each person’s disease. Thus, no two cancers are absolutely identical. The same type of cancer (for example, myeloma or leukemia) is different for each individual.

Therefore, in order to determine the most effective treatment for an individual patient, it is very important to identify the unique characteristics of each person’s disease, including mutations and patterns of gene expression.

At the Myeloma Center we utilize a full array of standard diagnostic tools, such as blood profiling, Magnetic Resonance Imaging (MRI), skeletal survey, bone densitometry, Positron Emission Tomography-Computed Tomography (CT/PET), bone marrow biopsy and more.

In addition, we utilize genetic testing at the molecular level to reveal information about gene expression patterns and disease nuances. This helps us predict how myeloma cells are likely to respond to different therapeutic agents and strategies.

Gene Expression Profiling

The Myeloma Center pioneered the routine use of gene expression profiling (GEP) to uncover important information about myeloma biology.
Based on GEP studies of more than 1,300 newly diagnosed patients, our researchers:

  • Identified a set of four genes that allows us to predict with high probability which patients are likely to progress from MGUS (monoclonal gammopathy of undetermined significance, a precursor condition) to myeloma
  • Developed a 70-gene test (GEP70) that identifies patients with high risk for short progression-free survival.
  • Identified seven distinct molecular subtypes of myeloma.
  • Identified mutations that affect response to therapy.

GEP studies are conducted at time of diagnosis and at various points throughout treatment.

Gene expression profiling makes it possible to predict with significant accuracy how a patient will respond to treatment. Myeloma Center physicians select treatment plans with the best potential for curative outcome, based on the individual’s genetic profile.

Genomics

Genomics refers to the study of genes and their functions. While genetics scrutinizes the functioning and composition of the single gene, genomics addresses all genes and their inter-relationships in order to identify their combined influence on the growth and development of cells.

Through advances in genomics, the Myeloma Center conducts studies that reveal high-level information for fine-tuning diagnosis and developing “precision medicine” treatments.

Specifically, we use DNA and RNA sequencing methods to look for a range of mutations that can help us target treatment. The data can inform us of treatment strategies and can help us identify approaches for cure. We also use Methylation Analysis to guide treatments that target tumor suppressor genes.

DNA Sequencing

DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. It includes any method or technology that is used to determine the order of the four bases—adenine, guanine, cytosine and thymine – in a strand of DNA. The development of rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery.

The first DNA sequences were obtained in the early 1970s through laborious methods based on two-dimensional chromatography. Following the development of fluorescence-based sequencing methods with automated analysis, DNA sequencing has become much easier and faster.
Next-generation sequencing, via high-throughput technology, enables sequencing of multiple genes and samples at one time. The technologies parallelize the sequencing process, producing thousands or millions of sequences concurrently.

RNA Sequencing

RNA Sequencing is a technology that uses the capabilities of next-generation sequencing to reveal the mutations causing myeloma that can be targeted with specific therapies. It can also be used to understand the level at which a gene is turned into a protein.
Genomic-based Sequencing Studies at the Myeloma Center include

  • Targeted Sequencing
  • Whole Exome Sequencing
  • RNA Sequencing
  • Whole Genome Sequencing

Methylation Analysis

DNA methylation is a chemical reaction that places a methyl group (combination of carbon and hydrogen atoms) at a particular spot on DNA. It can cause tumor suppressor genes that keep cell behavior normal to be switched off during myeloma progression.

Methylation Analysis provides insight for switching the tumor suppressor genes back on through the use of epigenetic treatments in order to normalize DNA packing and cell behavior.

Epigenetics refers to the way DNA is packed and wound into chromosomes and modifications to the genome that influence when and how often a gene is active.

Benefits of Advanced Diagnostics

Information obtained from advanced diagnostic testing, including Gene Expression Profiling and DNA and RNA sequencing, allows us to develop precision medicine approaches based on incorporating targeted therapies that are individualized for each patient.

The information supports development of prevention and early intervention strategies.

Understanding this information enables us to:

  • Design methods for normalizing cell biology that has gone astray and preventing disease progression.
  • Design treatment regimens based on altering the cell’s behavior to prevent resistance to therapy and disease relapse.
  • Design treatment strategies aimed at switching off the genetic signals that lead to myeloma development.
  • Identify additional mutations that could initiate cancerous activity in cells.
    Cure more patients with less toxic treatments.

Advanced diagnostics make it possible to predict which patients will benefit from a given drug.

Prognosis: Cure is Achievable

With our robust diagnostic capabilities and a state-of-the-art laboratory dedicated to molecular diagnostics discovery, we are well equipped to define the nuances of each patient’s disease. This, in turn, allows us to develop individualized treatment regimens for optimal effectiveness and, ultimately, cure for patients with myeloma and related diseases.[/fusion_text]

Winthrop P. Rockefeller Cancer Institute LogoWinthrop P. Rockefeller Cancer InstituteWinthrop P. Rockefeller Cancer Institute
Address: 449 Jack Stephens Dr., Little Rock, AR 72205
Parking Deck: 4018 W Capitol Ave., Little Rock, AR 72205
New Appointments: (501) 686-7105
Information Line: (501) 804-3557
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