Genetics

Multiple Myeloma: Genetic Study

Multiple myeloma (MM) is a hematologic cancer that affects plasma cells in the bone marrow, and chromosomal alterations are central to its diagnosis and prognosis. Genetic abnormalities include primary changes such as IGH gene rearrangements and secondary changes such as TP53 deletion, which influence survival and response to treatment. Prognosis is calculated using the international staging system (ISS), which is based on factors such as β2-microglobulin and albumin levels. Over time, revisions to the ISS have been developed to improve prognostic accuracy. The R-ISS adds the analysis of high-risk cytogenetic alterations such as t(4; 14), t(14; 16) and del(17p). Recently, the R2-ISS version incorporated the 1q gain alteration as a high-risk factor. These revisions help to tailor therapeutic strategies and improve patient outcomes. A key tool to identify these alterations is the fluorescence in situ hybridization (FISH) technique, which allows the detection of specific chromosomal abnormalities in plasma cells. At Catlab we perform the MultiFISH technique, which facilitates the analysis of the most relevant genetic alterations at once, improving diagnosis and personalization of treatment. In summary, the MultiFISH technique facilitates the detection of specific chromosomal alterations and guides the risk stratification,to provide personalized treatments and improve therapeutic response in patients with multiple myeloma.

Genetic study of MGMT gene promoter methylation in glioblastoma multiforme.

Glioblastoma multiforme(GBM)is an aggressive type of brain tumor with a poor prognosis. The usual chemotherapy treatment with temozolomide (TMZ) is more effective in patients with a methylated MGMT gene promoter. The MGMT gene encodes an enzyme with a DNA repair function, and the inactivation of this gene through methylation, results in tumors being more sensitive to alkylating agents such as TMZ.

At CATLAB, we have recently incorporated the study of the methylation status of the MGMT gene promoter, using real-time PCR in tissue samples preserved in paraffin, treated with bisulfite. The presence of methylation indicates a greater response to chemotherapy and a better prognosis, while the absence of methylation predicts resistance to therapy.

This test helps to personalize treatment and improve therapeutic decisions for patients with GBM.

Optimization of time and improvement in quality in the genetics service by automating tests with the ELITe InGenius analyzer

Genetics protocols are normally characterized by high complexity and multiple manual processes. Many of these protocols, such as those based on real-time polymerase chain reaction (qPCR), are similar to those used in the Molecular Microbiology section. Taking advantage of the fact that this section made progress in the acquisition of automated equipment due to the SARS-CoV-2 pandemic, the genetics section has proceeded to integrate a part of our activity into this equipment, achieving a substantial improvement in terms of reduction of response times, a reduction in both technical and medical dedication time, lower risk of pre- and post-analytical errors and better traceability of the entire procedure.

Informed consent for genetic studies: array-CGH and exome sequencing

Genetic studies available nowadays provide a large amount of information, which can be complex, difficult to understand and assimilate.

In the genetics area of Catlab we have written a complete document, approved by the Healthcare Ethics Committee of the Mutua de Terrassa University Hospital, which contains the necessary information to guide both doctors and patients. This document also contains the consent itself, which must be signed, prior to obtaining the samples and their analysis, by both the patient and the health professional.

This document will be available to all professionals through HCIS, and will be recorded in the patient's medical history.

Information for patients: Genetic testing

Catlab's Genetics department has produced an informative note aimed at patients, which briefly but clearly explains what a genetic study consists of, which sample is suitable and which methods currently exist.

Likewise, patients will also find information related to result interpretation and the advantages of carrying out these studies.

Hexanucleotide expansion in C9orf72 gene, associated with frontotemporal dementia and amyotrophic lateral sclerosis

Frontotemporal Dementia (FTD) is considered one of the most common forms of dementia in the population under the age of 65, with a prevalence of 10 cases per 100,000. Patients with DFT suffer a degeneration of the neurons in the frontal and temporal lobes that leads to changes in behavior and personality, deficits in executive functions and language deficiencies. The expansion of the C9orf72 gene is considered the most common hereditary genetic cause for both diseases. This article describes the study for this expansion at Catlab.

GENETICS - Array CGH in neurodevelopmental pathologies

The prevalence of neurodevelopmental pathologies in the general population is estimated at 1-3%. Genetic testing allows a more accurate prognosis. Today, conventional chromosomal analysis has been replaced by array comparative genomic hybridization (aCGH) techniques. At Catlab, since 2014 studies with the aCGH technique have been carried out, achieving good diagnostic performance. The good results are the product of the close relationship with the clinicians, the joint work in the diagnostic orientation, and the approach to be followed in each case, with the added value of the orientation towards the family counseling.

GENETICS - Pharmacogenetic study of the variants of the DPYD Gene in cancer patients

Fluoropyrimidines are anticancer compounds that act as antimetabolites in chemotherapies of different tumors. Its administration has to be controlled very well, since an excess of metabolites can trigger toxicity. The elimination of these metabolites is mainly controlled by the activity of the DPD enzyme. The DPYD gene encodes the DPD enzyme. It is a highly polymorphic gene, and the detection of the variants allows to predict the enzymatic activity before starting the treatment, thus preventing the adverse effects of DPD deficiency. Thus, based on the variants found, a calculation is made of the patient's ability to metabolize fluoropyrimidines. With this, we can categorize the patients according to the metabolization capacity, and the standard drug dose can be corrected and personalized.

GENETICS - Study of rearrangements in microsatellite instability of tumor DNA

The mismatch repair system (MMR) repairs small sequence errors, produced in DNA replication. Certain tumor subtypes present as a trigger mechanism a defect in the MMR genes, which gives them a biological behavior and a different prognosis to other tumors of the same tissues. This defect manifests itself at the molecular level as an instability in the size of gene regions called microsatellites. In Catlab, the analysis of five microsatellite regions is performed, using PCR and capillary electrophoresis on paraffin samples of tumor tissue, as a marker of MMR system deficiency.

EXTRA-ANALYTIC - Screening of aneuploidies in maternal blood

This November, the new Pregnancy Protocol was launched, which includes the screening of aneuploidy in maternal blood. It allows DNA detection of the fetus in the mother's blood from week 12, for women, in which biochemical screening is high risk and intermediate risk. Screening consists in the detection of numerical anomalies of chromosomes 13,18 and 21. That is, detection of Down Syndrome (Trisomy 21), Edwards Syndrome (Trisomy 18) and Patau Syndrome (Trisomy 13).