Diagnostic Genomics

The Cytogenetics & Molecular Cytogenetics Section provides a wide spectrum of genetic tests for constitutional and acquired (cancer) chromosomal alterations. Using various sample types such as blood, cord blood, amniotic fluid, Chorionic Villi, leukemic blood, bone marrow, skin biopsy, and tissue or products of conception, the section offers comprehensive testing in four main categories:

• Conventional Chromosomal Karyotyping:

  Conventional karyotyping is offered to detect chromosomal abnormalities in constitutional and cancer samples.

  1. Constitutional Chromosomal Karyotyping:

     The test includes screening for genetic disorders of congenital anomalies, aneuploidy, advanced maternal age, abnormal child development, Infertility, Amenorrhea, family history, and recurrent miscarriages.

     Our section also provides chromosome breakage analysis to assess genome instability. The most common syndrome for which this test is diagnostic is Fanconi Anemia (FA). FA is characterized by bone marrow failure, physical abnormalities, organ defects, and an increased risk of certain cancers. Chromosome breakage analysis is performed on different types of samples such as peripheral blood, bone marrow, skin biopsies.

  2. Hemato-oncology Chromosomal Karyotyping:

     The section offers Hemato-oncology cytogenetic analysis and plays an essential role in the diagnosis and classification of hematologic malignancies such as leukemia, lymphoma, myeloma. This test helps to define specific disease entities, provides important prognostic and predictive information, influences therapy decisions for personalized medicine options and assesses therapy effectiveness by indicating genetic remission or progression.

• Array Comparative Genomic Hybridization (aCGH) /Chromosomal Microarray Analysis (CMA):

  The section is equipped with CMA technology, a high-resolution whole genome test that identifies copy number variants (CNVs). CMA has been recommended as the first-tier genetic test for patients with developmental disabilities or congenital abnormalities, as it significantly increases the diagnostic yield of children affected with developmental delay, autism spectrum disorders, or multiple congenital abnormalities. CMA is offered for prenatal screening and postnatal diagnostics.

• Fluorescent in situ hybridization (FISH):

  Utilizing over 60 FISH probes, our section uses this technology for the detection of genetic aberrations in Constitutional, Oncology, and FFPE samples.

  1. Constitutional FISH test is used for prenatal/postnatal cases with various conditions including Chromosomal Aneuploidies, Williams, Prader-Willi, Angelman, SRY, and DiGeorge syndromes.
  2. Oncology and FFPE FISH tests are offered for the detection of a wide range of other cancers including Leukemia, Lymphoma, Myeloma, Lymphocytic Leukemia, Eosinophilia, Myeloid Dysplasia, Breast Cancer, Lung Cancer, Sarcomas, Liposarcomas, and Oligodendrogliomas.
• Noninvasive prenatal testing (NIPT):

  NIPT is a screening test offered during pregnancy to see if the fetus is at risk for having a chromosomal disorder such as trisomies: trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome); and Sex chromosome conditions: Turner syndrome, Klinefelter syndrome, Triple X syndrome and XYY syndrome. This noninvasive screening test is performed on the mother’s blood which contains fragments of DNA from the fetus and can be done as early as 10 weeks of pregnancy through delivery.

This section is the diagnostic service provider for the prevalent constitutional disorders of Qatar’s population. The tests are in the following four categories:

1. Postnatal Diagnosis

   The section offers diagnostic tests for twenty prevalent disorders of the population, such as, FMR1-related primary ovarian insufficiency, Y-Chromosome microdeletions, Prader-Will and Angelman Syndromes, alpha-thalassemia, Wilson Disease, Arterial tortuosity syndrome.

2. Prenatal Diagnosis

   Prenatal diagnosis is performed on chorionic villus samples (CVS) and amniotic fluid specimens for disorders such as beta-thalassemia, sickle cell anemia, spinal muscular atrophy.

3. National Premarital Genetic Screening Program

   The screening program is primarily for three prevalent disorders of Qatari population (Cystic Fibrosis, Homocystinuria and Spinal Muscular Dystrophy) with additional confirmatory tests for hematological disorders.

This section offers comprehensive genomic analysis of samples from patients with a range of hematological malignancies and lymphoproliferative conditions. Our testing focuses on diagnosis and classification, provision of prognostic information for use in risk stratification and assessment of residual disease status post-treatment and/or post-transplant. We offer testing of blood, bone marrow and FFPE sample types.

Genomic Testing in Acute Myeloid Leukemia (AML)

Samples referred for AML are activated for rapid FLT3-ITD and NPM1 fragment analysis, FISH, G band chromosome analysis and next generation sequencing using a panel of 33 myeloid genes. The results are reported based on WHO definitions and ELN risk stratification criteria.

NGS 33 gene panel content for AML

Following initial presentation, samples with suitable molecular markers are assessed for measurable residual disease using RTqPCR (PML::RARA, RUNX1::RUNX1T1, CBFB::MYH11, BCR::ABL1)

Genomic Testing in Chronic Myeloid Leukemia (CML)

RT-PCR analysis is performed to confirm or exclude a BCR::ABL1 arrangement in samples referred with suspected CML and to establish the BCR::ABL1 transcript type in a confirmed diagnosis. Patients with common e13a2 and e14a2 BCR::ABL1 transcripts are monitored by RT-qPCR of blood according to the schedule advised within the BSH 2020 guidelines. Results are expressed on the International Scale (IS) and the molecular response (MR) level is reported.

Genomic Testing in Myeloproliferative Neoplasms (MPN)

Samples referred with polycythemia rubra vera (PRV), essential thrombocythemia (ET), myelofibrosis (MF) are routinely tested for JAK2 V617F and CALR exon 9 mutations.

On reporting a negative result, NGS panel testing can be initiated depending on the degree of suspicion of MPN. Chromosome analysis is not routinely performed in MPN due to the very low abnormality rates and is not attempted on blood.

Where progression/transformation to AML is suspected, samples will be treated as per the AML pathway.

Genomic Testing in Chronic Lymphocytic Leukemia (CLL)

In addition to karyotype analysis, CLL patients are tested for TP53 deletions by FISH.TP53 mutation is assessed by next generation sequencing (NGS) analysis on request as chemo-immunotherapy is ineffective in patients with TP53 disruption allowing for alternative treatments to be considered.

Clonality testing for immunoglobulin (IGH) and T cell receptor (TCR) is also available for the diagnosis of lymphoproliferative diseases.

• Hereditary cancers
  • Full sequencing of BRCA1 and BRCA2 genes
     This section is currently offering full sequencing of BRCA1 and BRCA2 genes for eligible patients affected with breast, ovarian, prostate, pancreatic, and gastric cancers and melanoma. As certain drugs and treatments appear to be more effective in patients with abnormal BRCA genes, this test allows positive patients to benefit from precision or personalized medicine.
    
    We also offer BRCA1 and BRCA2 screening to unaffected individuals with a strong family history of BRCA-related tumors. Positive individuals benefit from preventive measures to reduce their risk for cancer and/or regular surveillance with the aim of detecting cancer at early stage, when it is most treatable.
    
    
  • Predictive testing
    We also offer predictive testing for unaffected individuals who are at-risk of inheriting a known familial pathogenic/likely pathogenic variant in BRCA1 or BRCA2 gene.
    

This section provides a comprehensive molecular biomarker testing, from a single gene to gene panels, using different molecular genetics technologies for all types of solid cancers. These include but are not limited to lung cancers, colorectal cancers, gastrointestinal stromal tumors, breast and ovarian cancers, thyroid cancers, melanomas, endometrial cancers, sarcomas and brain tumors.

The section is the first precision medicine laboratory for solid tumors in the State of Qatar, providing pre-disposition, predictive, diagnostic, prognostic testing and follow up. The section complies with guidelines from the National Comprehensive Cancer Network (NCCN).

The section utilizes advanced technologies such as real-time PCR, Sanger Sequencing and Next Generation Sequencing (NGS) for screening of over 300 genes and the detection of over 6000 variants including hotspots, small deletions and insertions, full gene sequencing, and copy number variations using DNA extracted from FFPE tumor samples. In addition, we perform identification of several fusion driver genes using RNA samples. ​​​​