PLATFORM MOLECULAR DIAGNOSTICS UZ GHENT (MDG)

For the analysis of specific somatic defects in the DNA and RNA of malignant tissue, blood or bone marrow of cancer patients, a collaboration is set up between three laboratories of Ghent University Hospital (Department of Pathological Anatomy UZ Ghent, Clinical Biology Laboratory UZ Ghent and Center for Medical Genetics Ghent) under the platform Molecular Diagnostics UZ Ghent (MDG). The platform Molecular Diagnostics UZ Ghent (MDG) combines the expertise of the three laboratories: the tests are requested through the Department of Pathological Anatomy UZ Ghent or through the Laboratory of Clinical Biology UZ Ghent, the laboratory tests are performed at the Center for Medical Genetics Ghent.

The core activity of MDG is the detection of acquired defects in DNA and RNA from the malignant tissues, blood or bone marrow of patients with cancer. With the detection of specific somatic defects in the tumors, a genetic fingerprint of the tumor is determined. This enables to make an accurate diagnosis, to refine a prognosis and/or identify a group of patients for targeted therpay. Targeted therapy is a breakthrough in oncology: for patients in the target group, the response to treatment is greater than the response to treatment with nonselective chemotherapy. Examples of clinical use include imatinib (Glivec) in gastrointestinal stromal tumors (GIST), cetuximab (Erbitux) and panitumumumab (Vectibix) in wild-type RAS metastatic colorectal carcinoma, and vemurafenib (Zelboraf) in BRAF-mutated melanoma.

The DNA NGS SOLID TUMOR panel and the DNA NGS HEMATO panel are accredited (*) NGS assays, the technique is a DNA, capture-based massive parallel sequencing.

The DNA NGS SOLID TUMOR panel detects single nucleotide variants (SNVs) and indels in 112 genes in samples of solid tumors and sarcomas. The DNA NGS HEMATO panel detects SNVs and indels in 116 genes in samples from hemato-oncological disorders including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), myeloproliferative disorders (MPN) and chronic lymphoid leukemia (CLL). The MDG-MPN1-mini test (3 genes) is a DNA-based assay that detects SNVs and indels in MPN samples via PCR-based massive parallel sequencing.

In addition, for glioblastomas, an assay is routinely performed for the analysis of methylation of the promoter of the MGMT gene.

For detection of fusions and splice variants there is an accredited (*) RNA NGS assay. This is an amplicon-based massive parallel sequencing flow with 4 different panels (SOLID TUMOR, SARCOOM, ALL and HEME).

The RNA NGS SOLID TUMOR panel includes 26 genes for detection of fusions and splice variants in solid tumors. The RNA NGS SARCOMA panel includes 55 genes for detection of fusions and splice variants in sarcomas. The RNA NGS ALL panel includes 64 genes for detection of fusions and splice variants in acute lymphoid leukemia (ALL). The RNA NGS HEME panel includes 87 genes for detection of fusions and splice variants in acute myeloid leukemia (AML).

(*) Ghent University, Ghent University Hospital, Center for Medical Genetics is accredited by BELAC under certificate number 351-MED (testing for solid tumors and sarcoma) and Ghent University, Ghent University Hospital, Clinical Biology Laboratory is accredited by BELAC under certificate number 087-MED (testing for hemato-oncological disorders).

(1) For the examination of somatic mutations in solid tumors and sarcomas, the tumor tissue in FFPE should be sent to the Department of Pathological Anatomy UZ Ghent. Here, the FFPE sections are made and the tumor percentage is determined.

To do this, use the request form of the Pathological Anatomy department: https://www.uzgent.be/pathologische-onderzoeken-aanvragen --> choose Request form “Aanvraagformulier moleculair pathologisch onderzoek”. The guidelines can be found on the website of the Pathological Anatomy department. In exceptional cases, fresh or frozen tumor tissue can also be sent to Center Medical Genetics. Sample instructions and request form can be found via acquired genetic disorders (https://www.cmgg.be/nl/zorgverlener/labguide/verworven-genetische-afwijkingen).

(2) For the examination of somatic mutations in blood or bone marrow of patients with hemato-oncologic disease, send the patient's blood or bone marrow to the Clinical Biology Laboratory UZ Ghent, together with a correctly completed request form, found at https://labgids.uzgent.be/--> Choose 'Request forms', choose 'Request form special hematology - cytomorphology | immunophenotyping | molecular analyses'. There you can also find the guidelines and background information (information about the genes under investigation).DNA/RNA isolation and reporting of test results is done by the Clinical Biology Laboratory of UZ Gent.

Furthermore, collaborations for clinical trials can be set up with MDG