Clinical AreaOncology

Here you will find the disease-related gene panels available for the clinical area specified above.

If you cannot find the disease you are looking for, please use a known synonym in the search (also in English).

Oncogenetic diagnostics are used to clarify the hereditary causes of cancer. The aim here is to detect deviations from the reference genome ("wild type") and then, if necessary, to distinguish between neutral variants and pathogenic mutations that are important for the physiological development and undisturbed function of all normal cells and their possible degeneration. The inheritance patterns of oncogenetic diseases are the basis of genetic counselling for patients, persons at risk and affected families. In the last 30 years, several hundred genes have been characterized which cause oncogenetic diseases or contribute to the development of cancer. Current results of oncogenetic research have a direct impact on the diagnostic procedure in the laboratory and genetic counselling. For example, mutations in independent genes on different chromosomes can cause clinically indistinguishable, hereditary forms of tumours such as Lynch syndrome ("locus heterogeneity"). On the other hand, different mutations in the same gene lead to clinically apparently separate disease entities (MSH2 gene mutations cause Lynch and Muir-Torre syndrome; TGFBR2 gene mutations cause Loeys-Dietz syndrome and HNPCC type 6; “allelic heterogeneity”).

Formal genetically and etiologically the following groups of oncogenetic diseases can be distinguished:

• monogenic diseases (autosomal or X-chromosomal inheritance)
• digenic diseases, which are only manifested when mutations are simultaneously present in heterozygous state in two different genes. The two normal gene products together form functional heterodimers. Digenic inheritance affects 3% of hereditary diseases in addition to the classic autosomal and X-linked diseases.
• mitochondrial diseases (maternal or autosomal inheritance)
• multifactorial diseases (interaction of several to many genes plus environmental factors)

Degenerate cells or congenital tumours often develop sporadically - is there a genetic (co-)cause? Inherited oncological diseases are demonstrably based on genetic changes and lead to disorders in the proteins that build up the cells, tissues and organs. DNA diagnostics therefore often involves a step-by-step procedure in which the most frequent mutations are first tested before the very rare genetic causes are also identified in parallel approaches using more expanded and cost-intensive panel procedures. Mutations found or all variants with unclear significance (VUS) are verified by DNA sequence analysis using the Sanger technique. Many tumor diseases are treated within the specific medical disciplines. Therefore, only some of the other more common disease groups are listed below.

In paediatric oncology, acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) and Ewing's sarcoma are the most prominent, in addition to the tumours discussed in other disciplines such as ophthalmology for retinoblastoma. Ewing's sarcomas are primitive neuroectodermal tumors with partly very different morphology, caused by many different translocations of the EWS gene on chromosome 22q12. Also in almost all CML patients a chromosomal translocation, the Philadelphia chromosome, can be detected as (co-)cause. In AMLs, the range of genetic alterations is wider, so that a more extensive gene panel is available. If necessary, only those genes that appear to be more closely associated with the clinical picture are initially analyzed. For further differential diagnostic questions, gene panels could also be applied in combination.

Patients with acute lymphoblastic leukemia (ALL) have many immature, dysfunctional lymphocytes; these lymphoblasts do not differentiate further. ALL subtypes include leukaemias of the B-cell or T-cell type. Philadelphia chromosomes are detected in some patients, and a panel is available for the other gene mutations that are observed. In adult AML, myeloid blasts do not mature further. For the classification into further subtypes, characteristic genetic changes of the genes contained in the panel are decisive or, in the case of AML, it remains "without further (genetic) classification possibilities". CML also belongs to the group of myeloproliferative neoplasias characterized by myeloblasts, usually with certain genetic alterations such as the Philadelphia chromosome.

In myelodysplastic syndromes (MDS), a myeloid progenitor cell changes, does not mature and can develop into leukaemia; the MDS can turn into AML. In MDS, many different somatic mutations ars observed, which can be directly analyzed together in a gene panel. As a malignant lymphoma, chronic lymphatic leukaemia (CLL) is not really a leukaemia. In CLL, mature lymphocytes change and exhibit specific somatic mutations that can be detected in the panel. For many of the abovementioned and many other diseases of this extended leukaemic form, the somatic gene changes (and possibly also inheritance patterns) are known, and the genetic defects can be directly detected. If the clinical diagnosis remains less specific, several gene panels are also available for differential diagnosis depending on the disease group.

Primary myelofibrosis (PMF) belongs to the group of chronic myeloproliferative neoplasias, it is a biologically and clinically very heterogeneous disease. PMF develops at the level of hematopoietic stem cells. The most frequent genetic aberration in myelofibrosis is the mutation V617F (amino acid valine at position 617 of the protein exchanged for phenylalanine) in the JAK2 gene of activated Janus kinase-2, followed by calreticulin (CALR) and thrombopoietin receptor (MPL) mutations. The demonstration of disease-associated somatic gene mutations ("driver mutations") allows to distinguish several molecular subtypes.

Lymphomas comprise various malignant tumours that develop from cells of the lymphatic system. In principle, there is a distinction between non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (see below). NHL include: diffuse large cell B-cell lymphoma, extranodal marginal zone lymphoma (MALT lymphom), mantle cell lymphoma, follicular lymphoma, Waldenström's disease (lymphoplasmocytic lymphoma), peripheral T-cell lymphoma, nodal marginal zone lymphoma. Diagnostic gene panels for different lymphoma categories include different numbers of (5-21 and more) genes, which are sequenced in parallel. First, those genes are analyzed that appear to be more closely associated with the clinical picture. For diagnostic purposes the individual gene panels can be used separately or in combination.