History of genomic testing at AUBMC Legacy

• The Molecular Diagnostics Laboratory has been established at AUBMC in 2001. Since then, it has only been growing to become the major referral center for genomic and molecular profiling in Lebanon and one of the leading centers in the region with the largest test menu.

• The Molecular Diagnostics Laboratory at AUBMC is equipped with state-of-the-art technology ranging from basic polymerase chain reaction (PCR) platform setting to the highest available sequencing technology from Sanger to Next Generation Sequencing.

• The Molecular Diagnostics Laboratory covers Molecular Pathology, Molecular Genetics, Molecular Microbiology, and Histocompatibility (HLA). It serves the oncology population of patients at the best through providing the largest test menu needed for diagnosis, prognosis, and treatment selection.

Mission

• Our mission is to offer our cancer patients up-to-date genomic and genetic profiling in an aim to optimize their care and provide them with the novel targeted therapeutics to enhance ultimate patient outcomes.

• We strive to reach our goals through relying on the latest and most updated state-of-the-art technology in the field of molecular diagnostics.

Vision

• The program is working to offer the MENA region cancer patients state-of-the-art genetic testing and Next Generation Sequencing in an aim to become a reference center for genomic profiling in the region while adopting all international standards and under the umbrella of our College of American Pathologists CAP-accredited diagnostic laboratories.

The Genomic Profiling Program benefits from 3 major service units:

•  Department of Pathology and Laboratory Medicine:

– Molecular Diagnostics Laboratory

– Medical Genetics Laboratory and its associated Genetic Counseling Unit

•  Basic Science Department at the Faculty of Medicine

– Basic Science laboratory services / Genetics Core Facility and Pillar Genetics Laboratory

•  Naef K. Basile Cancer Institute

The Genomic Profiling program offers the following services:

• Comprehensive Genomic Profiling
•  Predictive genetic testing

•  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.

– 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 and the type of pertinent treatment the cancer patient can benefit from.

– 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.

•  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 (CNAs)

· Rearrangements or fusions

•  This type of molecular testing produces a comprehensive patient report with a broad and deep assessment of possible underlying oncogenic (genes associated with cancer) drivers.

•  A single test can assess the most prevalent as well as rare biomarkers. Assessing all biomarkers at once increases the chances of finding an actionable alteration and improves treatment.

•  Genomic profiling integrates the detection of cancer biomarkers (genes, proteins, or other substances that reveal key details about a person’s cancer) into a single manifold assay, eliminating the need for multiple (sequential) testing.

•  Genomic profiling provides faster results and reduces the risks and cost associated with re-biopsy especially when access to additional tissue is not possible

•  Genomic profiling is now being performed on what we call “Liquid Biopsy” (like for example peripheral blood through circulating tumor DNA (ctDNA) instead of a biopsy from the tumor itself).

GENOMIC PROFILING FOR CANCER CELLS

•  Predictive genetic testing looks for hereditary gene defects that might put a person at a higher risk of getting certain types of cancer.

•  It helps you learn more about your cancer risk to prevent disease, improve treatment and survival.

•  It is available for certain types of cancers that might run in families such as: breast, ovarian, pancreatic, colon, and prostate cancers.

PREDICTIVE GENETIC TESTING FOR PATIENTS

•  Carrier screening for hemoglobinopathies is a type of test that checks whether you carry a gene for certain genetic blood disorders.

•  Screening allows you to find out your chances of having a child with a genetic blood disorder.

• Carrier screening for hemoglobinopathies is done with a blood test. There are two methods to test the blood sample:

– Hemoglobin electrophoresis: A test that looks at the different types of hemoglobin in your blood. It can show if the blood is abnormal.

– Molecular genetic testing: A test of the genes in your blood that checks for hemoglobinopathies and many other genetic disorders at the same time. This is also called expanded carrier screening.

Test results can be negative (not having the gene) or positive (having the gene).

•  Getting a carrier screening test before pregnancy gives you a greater range of options and more time to make decisions than testing during pregnancy.

•  Consult with a benign blood disease specialist at NKBCI who will refer you to a genetic counselor.

•  If you and your partner are both carriers, you should consult with a genetic counselor who can answer your questions and inform you more about options for having a healthy pregnancy.

• 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

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.

• Nada Assaf, MD

Instructor, Department of Pathology and Laboratory medicine

Medical Genetics division

Na167@aub.edu.lb, ext 5247

Dr Assaf is in charge of the Medical Genetics laboratory at the Department of Pathology and Laboratory medicine at the American University of Beirut Medical Center. Her expertise involves genetic testing for constitutional (including prenatal) and cancer disorders such as chromosomal banding analysis (karyotype), Fluorescent in Situ Hybridization (FISH) and Next Generation Sequencing (NGS). She is the author of multiple articles published in peer reviewed international journals, centered around hereditary cancers, and the genetic drivers of cancer.

Dr Assaf provides genetic counseling for patients and families with genetic disorders.

The newly established GENOMIC PROFILING PROGRAM welcomes patients. Consult with your NKBCI Hematology-Oncology physician for recommended referrals.

To schedule an appointment kindly contact the Naef K. Basile Cancer Institute on 01-350 000, Ext. 5800.

• Location: Aida and Halim Daniel Academic and Clinical Center ACC building, 5^th floor

• Date and Time: Weekdays from 8 am till 6 pm