•  It is always recommended to consult with the treating physician to assess whether full and large-scale genomic profiling is indicated for the patient’s case or not. Sometimes single or limited selected gene analysis may be enough.

•  Gene-mapping tests may be appropriate for patients with rare, unusual or hard-to-treat cancers, and for patients whose tumors metastasized or did not respond adequately to conventional therapies.

•  Genomic testing is recommended by the treating physician. When requested, please make sure to ask why it was a good idea to request the test. Test results will help diagnose and treat your cancer.

•  Although they both involve testing of genes, they don’t work exactly the same way:

Genomic testing looks at a larger number of your genes, rather than detecting a single gene mutation and associates the findings with other parameters.

Predictive genetic testing looks for inherited gene mutations that could affect your cancer risk.

– A genomic test looks more widely at what is called your genome — your full set of genetic “code”. It is used to check for gene mutations in your cancer to predict how it might respond to treatment or if it has probabilities for metastasis or recurrence.

– Genetic tests may help identify a person’s risk of cancer, but genomic testing helps identify the genetic markers (genes, proteins, or other substances) associated with the characteristics of the disease.

•  Predictive genetic testing looks for specific inherited gene mutations linked to an increased risk of cancer or other diseases. This information can help prevent disease, improve treatment course and ultimately increase survival. It is available for certain types of cancers that might run in families such as: breast, ovarian, pancreatic, colon, and prostate cancers. For breast cancer for ex, genetic tests can determine if the cancer is due to an inherited gene mutation. It can also help family members understand their risk of breast cancer and guide their screening tests at a possible earlier age. For example, if the breast cancer BRCA1 gene mutation runs in your family, your doctor might recommend that you get a genetic test. If you do test positive, you will know that you are at higher risk for breast cancer and you may need extra screening.

• Comprehensive genomic profiling: Can look at mutations across all the DNA in a cancer cell. Genomic testing is done on cancer cells to detect both the mutations in the tumor itself as well as mutations that the patient may have inherited. These tests are useful to determine the type of cancer, how aggressive it is how likely it is to spread, to recur and what treatment it could and mostly responds to. This information explains why some people develop more aggressive forms of cancer, or do not respond to certain forms of chemotherapy.

•  Genomic testing is now instrumental in treating and managing different types of cancer, including, but not limited to, breast cancer and lung cancer.

•  By helping to identify the genetic markers associated with the characteristic of the disease, Genomic profiling can offer both actionable and potentially actionable test results that make doctors more able to plan effective therapeutic paths and innovative clinical trial options for cancer patients.

•  Genomic testing can help identify:

– Risk markers to screen for cancer.

– Prognostic markers to predict how fast a cancer will progress, how likely it is to recur, and possibly the likely outcome.

– Predictive markers to guide treatment choices and avoid toxicity.

– Response markers to determine the efficacy of various treatments.

• When tissue biopsies are unavailable, genomic profiling from liquid biopsy may provide helpful information about a tumor’s genomic make-up. Profiling using tissue and liquid biopsy together may reveal more insights into a tumor’s composition.

• Liquid Biopsy is performed when tissue is not available for any reason (for example, if patient cannot undergo a re-biopsy or tumor has metastasized or recurred to a location that cannot be easily accessed) and is usually done on a peripheral blood specimen.

• Liquid Biopsy testing is also available at the American University of Beirut Medical Center.

Our expert physicians at the Naef K. Basile Cancer Institute help direct the patient to the appropriate indications and frequency of use of such liquid biopsy assays to help monitor your cancer.

•  Next-generation sequencing or NGS is the primary tool for genomic testing. NGS only uses a single assay to assess hundreds of genes including relevant cancer biomarkers.

•  It identifies and evaluates the genetic sequence of millions of short DNA segments called reads. The reads are then assembled (just like in a puzzle game) into a complete sequence to determine which genetic variations (variants) are present and what they mean.

•  Genomic testing is typically offered as a panel of targeted genes, ranging from an analysis of genetic “hot spots” (well-established sites of mutation) to full gene sequencing.

•  When a biopsy is taken from the patient’s tumor, the Pathology laboratory at the Department of Pathology and Laboratory Medicine studies the adequacy of the biopsy and confirms presence of an appropriate amount number of cancer cells to be studied and analyzed by more advanced tests. Later, the cancer cells’ DNA is extracted and processed to be sequenced in the Molecular Diagnostics and Sequencing Laboratory. Then, sophisticated equipment is used to scan the sequenced genetic profile for abnormalities that dictate how the tumor functions.

•  Once the sample is obtained, it usually takes around a week to receive the results.

•  With a single test or assay, Comprehensive Genomic Profiling can analyze a broad panel of genes to detect the four main classes of genomic alterations known to drive cancer growth:

– Base substitutions

– Insertions and deletions

– Copy number alterations

– Rearrangements or fusions

•  Next-generation sequencing is extremely flexible and can be used to sequence only a few genes, such as for a hereditary breast cancer panel (composed of few genes), or the whole genome used typically for research purposes to screen for rare diseases.

•  Depending on the cancer condition being treated, a genetic counselor may be on hand to help you understand the limitations of the test and what the results mean.

•  Test results are analyzed to help figure out which treatments are most likely to work best against your cancer. Matching the therapy to your genes makes your treatment more precise, which might also lower your chances of having side effects.

Tumor profiling tests can help predict:

– The behavior of a tumor

– How fast a tumor will grow

– How likely a tumor will metastasize

– How likely a tumor is to respond to a drug

•  This is important because the cells of a tumor can mutate rapidly. Even if a single genetic variant is responsible for a tumor, the disease itself can take many different courses, some aggressive and others not.

•  Whether targeted therapy will be recommended as treatment is a decision taken only by the treating physician and tailored to the results obtained by the Comprehensive Genomic Profiling results. Sometimes there will be indications for this type of therapy but other times sometimes there will be none.

To know more about genomic tests please visit the Department of Laboratory and Pathology Medicine

•  Cancer cells generally gain multiple types of chromosomal aberrations during tumor progression, including rearrangements, deletions, and duplications. As a result, the genome becomes progressively more unstable.

•  If identifiable mutations are found, they are analyzed to determine whether they match known mutations that may have responded to particular therapies or where evidence suggests there may be a potential treatment option not previously considered.

•  If there’s a match, doctors may be able to use the results to suggest treatments that have been used in the past to target the same mutations. In addition, they may suggest new treatment options depending on latest clinical and research studies related to the new types of therapy.

•  Despite the vast amount of data generated with genomic profiling and growing knowledge in genomics, many genes still have unknown roles, and many genomic variants or mutations have not been identified as not causing disease (benign) or causing disease (pathogenic).

•  The amount of information and testing methods available has grown greatly for certain genomic variations, but how clinically significant changes in risks are is not completely understood yet or the clinical pathway is unclear after finding the variation. Your physician will be discussing this information in full details upon completion of your genomic profiling tests.

•  Information gathered from patients’ genomes can be highly predictive of an increased risk for later cancer development or behavior but can also be linked to only slight increases in risk or point to variations not yet fully understood.

•  There are very few disease processes entirely dependent upon a single mutation. For cancer particularly there is a lot of interaction between different mutations, influencing the course of the disease and the likelihood that it will respond to treatment.

• Should a genetic variation be discovered during treatment, it may not be possible to tailor treatment because there is still so much to learn about these interactions.

•  In addition to the ethical, legal, and social issues surrounding genomic profiling, questions persist regarding the clinical utility, safety, and cost-effectiveness of genomics-based risk assessment.

• Genomic profiling carries ethical concerns particularly when testing leads to unexpected findings.

•  The best way to discover new therapeutic targets or mechanisms of medications is to compare the tumor’s DNA sequence with that of a patient’s normal tissue. This requires clinicians to perform a normal DNA sequence, which could uncover other inherited variations in an individual’s genome that are unrelated to cancer.

•  Finding one of these unexpected discoveries could raise the question whether the clinician is obligated to tell the patient and if it was information the patient would want to know or not. In any genetic testing scenario, information may be uncovered that a patient is not prepared to receive.

• A main issue is then to make sure the patient is appropriately informed before testing is done, and that he/she can understand the kind of results testing could produce so that he/she can decide if it is something they want to know.

• This is why, it is extremely important to have an informed consent signed prior to full and extensive large scale genomic testing that may produce genetic information that has implications on other members of the patient’s family.

• Genetic Counseling is a key player when such information is revealed and the service is also available at AUBMC through the Predictive Genetic Testing service.

• You can coordinate with your physician to get appropriate counseling in our institution with the Predictive Genetic Testing team.

• Rami Mahfouz, MD, MPH (LabM), IFCAP

Tenured Professor of Pathology and Laboratory Medicine

Head, Division of Clinical Pathology

Director, Molecular Diagnostics Laboratory

Director, Residency Training Program

Chair, Biomedical Institutional Review Board

Co-Director, Pillar Genomics Institute

American University of Beirut Medical Center Phase 1, Third floor, Room W-327

rm11@aub.edu.lb, ext 5167 5165

Recently elected as a Full Member of Sigma Xi, The Scientific Research Honor Society, in recognition of his noteworthy achievements in research, Dr. Mahfouz has joined a cadre of distinguished and committed researchers around the world. Sigma Xi is the world’s largest multidisciplinary honor society for scientists and engineers with a mission to enhance research and promote the public’s understanding of science for the purpose of improving the human condition.

He has made significant contributions to the scientific community through groundbreaking work in various fields, with a particular focus on cancer research and diagnosis: with more than 200 peer-reviewed publications to his name as the senior author published in high-impact journals.

In his illustrious career, Dr. Mahfouz has held numerous leadership positions: serving as the Director of the Molecular Diagnostics Laboratory and the Residency Training Program, as well as heading the Clinical Pathology Division within the Department of Pathology and Laboratory Medicine at AUBMC. Additionally, Dr. Mahfouz has played a pivotal role in shaping the future of genomics research as the Interim Director of the Pillar Genomics Institute (PGI). In recognition of his unwavering commitment to research, he was appointed as the Chair of the Institutional Review Board (IRB) in April 2022.