Undifferentiated pleomorphic sarcoma (UPS) is a diagnosis of exclusion; given limited effective treatments and marked heterogeneity, there is a need to identify therapeutic targets, a task facilitated Show more
Undifferentiated pleomorphic sarcoma (UPS) is a diagnosis of exclusion; given limited effective treatments and marked heterogeneity, there is a need to identify therapeutic targets, a task facilitated by next-generation sequencing (NGS) in clinical practice. We report 2 STS pts with the diagnosis of UPS, G3 - each treated in a clinical trial (NCT03651374) with UNRESARC protocol consisting of neoadjuvant chemotherapy (CHT), radiotherapy, and surgical resection. Biopsy samples from each patient were subjected to NGS with the TruSight™ Oncology 500 assay (Illumina) and analysed in PierianDX (commercial software). 5 pathogenic alterations were identified: Case A: CCNE1 (6 copies) and MYC (3 copies) amplifications; Case B: CCND1 (3 copies), EGFR (3 copies) and FGFR1 (4 copies) amplifications. Amplifications of cell-cycle associated (CCNE1, CCND1) and apoptosis-related (MYC) genes contribute to uncontrolled proliferation and resistance to apoptosis, while amplifications in receptor tyrosine kinases (EGFR and FGFR1) activate pathways (RAS/MAPK and PI3K/AKT), involved in tumour growth and metastasis. In both patients, a poor pathological response, early local recurrence (LRFS of 9 months in both patients) and progressive disease (PD) when treated with first-line palliative CHT (PFS of 5 months in A and 4 months in B) were noted. All tumours demonstrated a low tumour mutation burden (TMB) (1.6-3.9 mut/Mb) and no microsatellite instability (MSI), explaining no sensitivity to immune checkpoint inhibitors. NGS assays may enable accurate diagnosis and identify predictive biomarkers and novel therapeutic targets - of particular importance in poor-prognosis entities such as UPS. Our report is consistent with the literature classifying UPS as malignancy with a high frequency of CNAs and low TBM. Show less
Left ventricular non-compaction (LVNC) is still a pathology around which there are numerous controversies regarding the criteria for its diagnosis, presentation, prognosis, and even classification int Show more
Left ventricular non-compaction (LVNC) is still a pathology around which there are numerous controversies regarding the criteria for its diagnosis, presentation, prognosis, and even classification into the appropriate group of diseases. So far, about 190 genes in which mutations may be associated with LVNC have been described, and in each of them, several to several dozen different We retrospectively analyzed the results of cardiac magnetic resonance (CMR) studies. Twenty-three patients who met Petersen's criteria agreed to participate in the research and take blood samples for genetic testing. Next, we prospectively included 24 volunteers who did not meet Petersen's criteria. Petersen's criteria were complied with ratio of non-compacted to compacted myocardium (NC/C) ≥2.3. A total of 47 DNA samples were analyzed based on the selected regions of the following genes: β-myosin heavy chain ( In total, 248 substitutions in exons and introns were obtained for all analyzed samples. No statistically significant differences were detected between the mentioned groups. No significant difference in either downward or upward trends in the number of substitutions in relation to the increasing trabeculation is observed. We indicated differences in the occurrence of the studied SNVs between groups, especially for rs8037241 ( To our knowledge, no studies have been published comparing the prevalence of selected SNVs in a group of healthy subjects and in a group meeting the Petersen criteria for LVNC. Among both completely healthy individuals who did not meet the Petersen criteria for LVNC as well as those with symptoms who met these criteria we found a similar incidence of SNVs in the Show less