Implementation of the TP53 somatic variant detection for prognosis detection in case of chronic lymphocytic leukemia

The TP53 encoded protein is an important tumor suppressor. Somatic pathogenic variants in the TP53 in the case of chronic lymphocytic leukemia (CLL), the same as 17pdel, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. As result of genetic variant is affecting the treatment choice there is initiative from the Network of the European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) to harmonize the testing and reporting methodology. Aim was to implement the TP53 testing in Latvia for risk assessment in the CLL. In the study were included 10 patients with CLL diagnosis, and eight samples in the frame of external quality schemes (five samples from the ERIC network and three from Instand de). DNA was isolated using the phenol-chloroform method from whole blood with EDTA conservant. TP53 analysis was done using Sanger sequencing according to ERIC suggested protocol, variant interpretation was done using IUARC TP53, COSMIC, and other available databases. In 9 patients, there were not identified clinically important pathogenic variants with somatic mosaicism: >20% (detection limit for the Sanger sequencing). In one patient there was an identified variant - p.Ser215Ile. The patient has the CLL diagnosis in 2012, had received treatment. This was the first time when TP53 variants were tested for the patient, there were not detected 17p deletion. For the samples from the external quality schemes, there were samples with different TP53 genotypes that were correctly identified and interpreted according to quality standards. TP53 gene analysis is performed according to ERIC quality standards allowing to have more precise risk estimation for the CLL patients in Latvia.