The cancer-risk variant frequency among Polish population reported by the first national whole-genome sequencing study.

Introduction: Population-based cancer screening has raised many controversies in recent years, not only regarding the costs but also regarding the ethical nature and issues related to variant interpretation. Nowadays, genetic cancer screening standards are different in every country and usually encompass only individuals with a personal or family history of relevant cancer.

Methods: Here we performed a broad genetic screening for cancer-related rare germline variants on population data from the Thousand Polish Genomes database based on 1076 Polish unrelated individuals that underwent whole genome sequencing (WGS).

Essential thrombocythaemia progression to the fibrotic phase is associated with a decrease in JAK2 and PDL1 levels.

It has been postulated that the changes in the molecular characteristics of the malignant clone(s) and the abnormal activation of JAK-STAT signaling are responsible for myeloproliferative neoplasm progression to more advanced disease phases and the immune escape of the malignant clone. The continuous JAK-STAT pathway activation leads to enhanced activity of the promoter of CD274 coding programmed death-1 receptor ligand (PD-L1), increased PD-L1 level, and the immune escape of MPN cells. The aim of study was to evaluate the PDL1 mRNA and JAK2 mRNA level in molecularly defined essential thrombocythaemia (ET) patients (pts) during disease progression to post-ET- myelofibrosis (post-ET-MF).

Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia.

We aimed to identify miRNAs and pathways specifically deregulated in adolescent and young adult (AYA) T-ALL patients. Small RNA-seq showed no major differences between AYA and pediatric T-ALL, but it revealed downregulation of miR-143-3p in T-ALL patients. Prediction algorithms identified several known and putative oncogenes targeted by this miRNA, including , , and .

Gene Variants Related to Cardiovascular and Pulmonary Diseases May Correlate with Severe Outcome of COVID-19.

Severe outcomes of COVID-19 account for up to 15% of all cases. The study aims to check if any gene variants related to cardiovascular (CVD) and pulmonary diseases (PD) are correlated with a severe outcome of COVID-19 in a Polish cohort of COVID-19 patients. In this study, a subset of 747 samples from unrelated individuals collected across Poland in 2020 and 2021 was used and whole-genome sequencing was performed.

The Thousand Polish Genomes-A Database of Polish Variant Allele Frequencies.

Although Slavic populations account for over 4.5% of world inhabitants, no centralised, open-source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for clinical genetics, biomedical research, as well as archeological and historical studies.

SARS-CoV-2 infection activating a novel variant of the gene and subsequently causing development of CADASIL.

Introduction: In the following study we describe the diagnostic process and further case analysis of a 30-year-old woman admitted with typical COVID-19 symptoms, who subsequently developed additional symptoms suggesting cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL).

Material And Methods: Other than the standard diagnostic procedures, whole genome sequencing (WGS) was used, which led to following findings. A new variant of the gene, which led to CADASIL-like symptoms, was found, and it had been most likely activated by the SARS-CoV-2 infection.

New genetic variants of TET2 and ASXL1 identified by next generation sequencing and pyrosequencing in a patient with MDS-RS-MLD and secondary acute myeloid leukemia.

Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by the presence of cytopenias, ineffective hematopoiesis and frequent transformation into secondary acute myeloid leukemia (secAML). Recent genomic studies provide unprecedented insight into the molecular landscape of clonal proliferation in MDS. Genetic diversity of both MDS and secAML subclones cannot be defined by a single somatic mutation.

Validation of HER2 Status in Whole Genome Sequencing Data of Breast Cancers with the Ploidy-Corrected Copy Number Approach.

Background And Objective: Human epidermal growth factor receptor 2 (HER2) protein overexpression is one of the most significant biomarkers for breast cancer diagnostics, treatment prediction, and prognostics. The high accessibility of HER2 inhibitors in routine clinical practice directly translates into the diagnostic need for precise and robust marker identification. Even though multigene next-generation sequencing methodologies have slowly taken over the field of single-biomarker molecular tests, the copy number alterations such as amplification of the HER2-coding ERBB2 gene are hard to validate on next-generation sequencing platforms as they are characterized by chromosomal structural heterogeneity, polysomy, and genomic context of ploidy.

IDH2 mutations in patients with normal karyotype AML predict favorable responses to daunorubicin, cytarabine and cladribine regimen.

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) genes occur in about 20% patients with acute myeloid leukemia (AML), leading to DNA hypermethylation and epigenetic deregulation. We assessed the prognostic significance of IDH1/2 mutations (IDH1/2) in 398 AML patients with normal karyotype (NK-AML), treated with daunorubicine + cytarabine (DA), DA + cladribine (DAC), or DA + fludarabine. IDH2 mutation was an independent favorable prognostic factor for 4-year overall survival (OS) in total NK-AML population (p = 0.

Increased methylation upstream of the MEG3 promotor is observed in acute myeloid leukemia patients with better overall survival.

Background: The delta-like non-canonical Notch ligand 1 (DLK1)-maternally expressed 3(MEG3) locus (DLK1-MEG3 locus) plays a critical role in the maintenance and differentiation of hematopoietic stem cells. Accumulating evidence implicates the imprinted genes from this locus, DLK1 and MEG3, in the development and progression of acute myeloid leukemia (AML). However, the contribution of this locus to the treatment response of patients and their survival is unknown.

International external quality assurance of JAK2 V617F quantification.

External quality assurance (EQA) programs are vital to ensure high quality and standardized results in molecular diagnostics. It is important that EQA for quantitative analysis takes into account the variation in methodology. Results cannot be expected to be more accurate than limits of the technology used, and it is essential to recognize factors causing substantial outlier results.

The JAK2 V617F mutational status and allele burden may be related with the risk of venous thromboembolic events in patients with Philadelphia-negative myeloproliferative neoplasms.

Introduction: Patients with Philadelphia-negative myeloproliferative neoplasms (Ph(-) MPNs) are at increased risk of thromboembolic and hemorrhagic complications. The aim of the study was to determine the relationship between JAK2 V617F mutational status, JAK2 V617F allele burden and the risk of vascular complications occurrence.

Materials And Methods: Analysis was performed in a cohort of 186 patients diagnosed with polycythemia vera (53), essential thrombocythemia (114), primary myelofibrosis (11), and unclassified MPN (8).

Bleeding complications after arthroscopy in a JAK2V617F-positive patient with essential thrombocythemia and acquired von Willebrand syndrome (AVWS).

Acquired von Willebrand syndrome (AVWS) is an acquired bleeding disorder with clinical and laboratory features similar to those of the inherited form of the disease. AVWS is reported in many disorders, most frequently in myeloproliferative neoplasms and in, among others, essential thrombocythemia (ET). Interestingly, ET is associated with both the thrombotic and haemorrhagic complications, which occur in 20 % and 5-30 % of patients, respectively.

Frequency and molecular characteristics of calreticulin gene (CALR) mutations in patients with JAK2 -negative myeloproliferative neoplasms.

In 2013, Nangalia et al. and Klampfl et al. found a recurrent and abundant mutation in the calreticulin gene (CALR), mutually exclusive with JAK2 and MPL alterations.