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Glossary Blog, March 2018: Tumor Sequencing

Tumor Sequencing: A laboratory method that is used to determine the entire genetic makeup of specific tumor cell types by identifying the exact sequence (order) of the four building blocks, or bases, that make up its DNA. This method can be used to find changes in areas of the genome. These changes may help scientists understand how specific diseases, such as cancer, form. Results of genomic sequencing may also be used to diagnose and treat disease. 


DNA sequencing or testing, genetic/genomic sequencing, molecular sequencing, molecular analysis, tumor sequencing, molecular profiling, tumor analysis, etc. These terms, their technical semantics aside, all refer to essentially the same concept: scanning tumor cells for changes, or alterations, in its genetic and molecular makeup that are different from normal cells.

Basic Overview

Brain tumors and cancer arise when cells in the brain begin to grow and multiply out of control. Typically, changes in the DNA that direct how cells function is the culprit for this uncontrolled growth.

Each person’s tumor has a unique combination of genetic changes, and tumor DNA sequencing—sometimes referred to in one of the other ways mentioned above—is a test to identify these unique DNA changes. In some cases, knowledge of these alterations in your tumor can help determine a treatment plan.

Additionally, tumor sequencing is critical to researching the potential causes and/or drivers of tumors, so that new treatments can be developed.

For Diagnosis and Treatment

Tumor sequencing is the foundation of precision medicine: treatment tailored to the specific molecular/genetic characteristics of each patient’s tumor.

As cancer treatment increasingly moves toward a precision medicine approach that relies on understanding the specific biological, genetic, and molecular changes that happen within cells to drive an individual’s tumor growth, sequencing patients’ tumors is becoming increasingly important. To do so, patients’ tumor tissue is scanned for mutations or other abnormalities linked to cancer. The results of these scans can indicate patients who are good candidates for targeted therapies or for clinical trials in which potential new treatments are being tested.

Dr. Andrew Sloan, Director of the Brain Tumor and Neuro-Oncology Center at Case Western Reserve University School of Medicine said in 2015, after a study on molecular/genetic analysis and profiling of gliomas, that, “It can easily be implemented and will markedly improve diagnosis, patient care, and treatment planning.”

Tumor sequencing can tell doctors what genetic and molecular mutations or alterations are present in a patients tumor. This information can then be used to make a more accurate, specific diagnosis of the exact tumor-type, which will contribute to the planning of a patient’s treatment and care. Infomation from tumor sequencing can tell doctors, based on the mutations and alterations present, if the patient’s tumor is likely to be more aggressive, or slow growing, and thus if aggressive treatment is recommended. In some cases, it can also point to specific, targeted drugs that could be more effective than standard treatments for an individual patient’s tumor (if drugs already exist that are designed specifically to target the alterations or mutations in play). Finally, they can help determine if there are any clinical trials open for patients with the mutations of alterations in question that are evaluating potential new targeted therapies.

“This molecular data helps us better classify gliomas patients, so we can begin to understand who needs to be treated more aggressively and who might be able to avoid unnecessary therapies,” Dr. Daniel Lachance of the Mayo Clinic told NBC News in 2015 about data gleaned from analysing tumors at the genetic and molecular level.

For brain tumors, specifically, genetic and molecular analysis is growing in increasing importance following the updates in 2016 to the World Health Organization classifications for brain tumors.

Identifying tumors based on the specific mutation and alterations found in cells, “Will potentially allow us to predict the course of gliomas more accurately, treat them more effectively, and identify more clearly what causes them in the first place,” Dr. Margaret Wrensch of the University of California, San Francisco said in 2015.

More information on using tumor sequencing in brain tumor treatment can be found, here.

For Research

Tumor sequencing plays a major role in cancer research, as well. Projects such as The Cancer Genome Atlas (TCGA) have sequenced thousands of tumor tissue samples to help uncover which genetic irregularities drive the growth of various types of cancer, including glioblastoma – the first tumor-type the TCGA analyzed. Sequencing can also help researchers track how tumors change over time and/or after certain treatments have been applied. By sequencing the DNA in a tumor before and after treatment, for example, researchers hope to learn how it adapts to treatment and potentially becomes resistant to it. All of this work is necessary to, first, identify new targets to develop novel treatment strategies around, and then design medicines and drugs that can attack those targets.

Challenges and Considerations

Across the cancer landscape — and in brain tumors, particularly — we are still in the relative early-days of precision medicine and the ability to match patients to targeted or tailored treatments based on the specific irregularities found in their tumor. Unfortunately, at the present, there are not many mutations or other alterations found in brain tumors that are “actionable”- meaning essentially that there aren’t yet treatments designed to specifically target them. There have been anecdotal and case reports of individual brain tumor patients, whose tumor tested positive for a mutation also found in a different cancer for which there was a targeted drug available, and who responded well to such treatment. But on the whole, the lack of drugs designed specifically for the alterations often found in brain tumors limits our ability to use targeted therapies in the clinic on a widespread basis currently. That said, precision medicine-based research and clinical trials for brain tumors are very much happening in high-volume, and we hope to soon be able to reap the fruits of these efforts for patients in the clinic. Further, analysis of patients’ tumors – as noted above – can still be very important to diagnosis and treatment planning.

Finally, cost and insurance coverage for these types of tests are still a consideration for many individual patients. As the technologies and techniques used to perform tumor sequencing are relatively new, issues surrounding insurance coverage and reimbursement are still being hashed-out. The individual circumstances surrounding the potential use of tumor sequencing in the clinic will often determine if, and how, these tests will be covered by insurance (as well as your insurance plan itself). Patients should remember to consult with their doctors and their insurance provider if they have any questions or concerns related to performing these tests and their cost.

Resources/Sources & Further Reading

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/dna-sequencing

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/genomic-sequencing

https://www.cancer.gov/about-cancer/treatment/types/precision-medicine/tumor-dna-sequencing

http://braintumor.org/brain-tumor-information/genetic-testing/

https://www.illumina.com/areas-of-interest/cancer/research/sequencing-methods.html

http://blog.dana-farber.org/insight/2017/12/dna-sequencing-cancer-therapy/

http://time.com/4769503/cancer-tumors-dna/ 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557651/

https://www.npr.org/sections/health-shots/2018/01/15/572940706/for-now-sequencing-cancer-tumors-holds-more-promise-than-proof

https://www.technologyreview.com/s/601611/should-we-sequence-the-dna-of-every-cancer-patient/ 

https://labblog.uofmhealth.org/lab-report/comprehensive-sequencing-program-shows-promise-of-precision-medicine-for-advanced-cancer 

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