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Update from Mesothelioma Information
This extract in our series from the Program Report of the International Mesothelioma Program explains how IMPs use of . . .
Genomic Research Seeks to Enhance Mesothelioma Diagnosis, Prognosis, and Treatment
The Human Genome Project, completed in 2003, mapped the complete sequence of three billion chemical base pairs that make up human DNA and made them accessible for further biological study. This feat has helped researchers better understand how DNA is organized and structured and how it functions, and is a critical advance in improving our understanding of complex diseases such as mesothelioma.
"The exact number of human genes is still uncertain, but is likely to be at least 40,000," said Gavin Gordon, PhD, Assistant Professor at Harvard Medical School and member of the International Mesothelioma Program at Brigham and Women's Hospital. Gordon joined the laboratory of Raphael Bueno, MD, more than five years ago as a post-doctoral fellow. He participated in research elucidating the gene expession patterns in mesothelioma. He now co-directs the Thoracic Oncology Laboratory with Dr Bueno.
"In all cancers, and particularly mesothelioma," said Gordon, "many of these genes are not functioning correctly. Some genes, such as those that regulate cell growth, may be over-expressed while others that are critical to prevent the formation of tumors are not expressed at all. One of our goals is to identify these abnormally expressed genes so that we can develop better treatments for mesothelioma patients."
Another goal is to identify patterns of gene expression in patients' tumors that are predictive of how well a patient will respond to current therapy including surgery. "Obtaining this information prior to surgery will allow us to individually tailor therapy so that patients receive the treatment best suited to their particular type of mesothelioma," he said.
The technique used in the Bueno-Gordon Jab for measuring gene expression is microarray profiling analysis. Microarrays are small support structures or platforms, "pieces of glass about the size of a credit card, or smaller," said Gordon. With the assistance of robotics, sequences of DNA that correspond to tens of thousands of genes are imprinted onto the microarray platform and are used to probe and quantify the genes expressed by individual tumors. "In this way, we can simultaneously measure the expression levels of tens of thousands of genes in a single tumor," explains Gordon. "This, combined with our access to hundreds of mesothelioma patient tumors, will dramatically increase the speed at which we can identify abnormally expressed genes and gene patterns that correlate with clinical outcome."
Microarray expression profiling analysis has a number of potential benefits for patient care. Expression profiling can assist in identifying molecular markers for determining whether an abnormal growth is malignant or benign. It also can help predict which patients will respond favorably to the best available treatments and which are likely to not do well and would be candidates for other experimental treatments. "Expression levels of genes will play a part in designing better treatments for mesothelioma," said Gordon. "Many genes are expressed at high levels in tumor cells and low levels in normal cells and are driving the uncontrolled proliferation and growth of tumor cells. If we can knock out those highly expressed genes, we can make the tumor more amenable to chemotherapy for example."
The Bueno-Gordon lab also is conducting research that will help translate these discoveries into clinically relevant tests to impact patient care as rapidly as possible – for example, tests for cancer detection and diagnosis. Before these tests can be used in actual patients, however, it is critical to know their reproducibility and how informative they are under a variety of circumstances. For example, is a small bit of tissue taken from one area of a tumor the same as a sample taken from another area? How much tumor needs to be in a good specimen? Does the technique used in a biopsy matter? Another area of investigation involves the equipment itself: if a test is done today on machine #1, will the lab get the same results if that sample is tested tomorrow using machine #2?
"Ultimately, we want to make these tests available to other centers and for other populations," said Gordon. "So we need to know that the test will work as well for all patients as it does here in Boston. To answer these questions, we are collaborating with other physicians and scientists around the country."
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