Analysis of Intrinsic Breast Cancer Subtypes: The Clinical Utility of Epigenetic Biomarkers and <i>TP53</i> Mutation Status in Triple-Negative Cases

This study aimed at analyzing the DNA methylation pattern and TP53 mutation status of intrinsic breast cancer (BC) subtypes for improved characterization and survival prediction. DNA methylation of 17 genes was tested by methylation-specific PCR in 116 non-familial BRCA mutation-negative BC and 29 control noncancerous cases. At least one gene methylation was detected in all BC specimens and a 10-gene panel statistically significantly separated tumors from noncancerous breast tissues. Methylation of FILIP1L and MT1E was predominant in triple-negative (TN) BC, while other BC subtypes were characterized by RASSF1, PRKCB, MT1G, APC, and RUNX3 hypermethylation. TP53 mutation (TP53-mut) was found in 38% of sequenced samples and mainly affected TN BC cases (87%). Cox analysis revealed that TN status, age at diagnosis, and RUNX3 methylation are independent prognostic factors for overall survival (OS) in BC. The combinations of methylated biomarkers, RUNX3 with MT1E or FILIP1L, were also predictive for shorter OS, whereas methylated FILIP1L was predictive of a poor outcome in the TP53-mut subgroup. Therefore, DNA methylation patterns of specific genes significantly separate BC from noncancerous breast tissues and distinguishes TN cases from non-TN BC, whereas the combination of two-to-three epigenetic biomarkers can be an informative tool for BC outcome predictions

Uporaba 2-aminoprop-1-en-1,1,3-trikarbonitrila u sintezi derivata tetrahidronaftalena, heksahidroizokinolina i heksahidrocinolina s potencijalnim antitumorskim djelovanjem

The aim of the work was to synthesize heterocyclic compounds from 2-aminoprop-1-ene-1,1,3-tricarbonitrile and to study their antitumor activities. The title reagent reacted with cyclohexanone to give the ethylidene derivative 2. The reactivity of the latter product towards different reagents was studied to give tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives. The newly synthesized products were screened as antitumor agents on the in vitro growth of three human tumor cell lines representing different tumor types, namely, breast adenocarcinoma (MFC-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268). It was found that some of these compounds showed inhibitory effects on the three cell lines, indicating their potential use in the development of oncology products.Cilj rada bio je sintetizirati heterocikličke spojeve polazeći od 2-aminoprop-1-en-1,1,3-trikarbonitrila. Taj spoj je prvo u reakciji s cikloheksanonom dao derivat etilidena 2, iz kojeg su zatim priređeni derivati tetrahidronaftalena, heksahidrokinolina i heksahidrocinolina. Novosintetizirani spojevi ispitani su na antitumorsko djelovanje in vitro na tri humane tumorske stanične linije: adenokarcinoma grudi (MCF-7), tumora pluća (NCI-H460) i tumora CNS-a (SF-268). Neki od ispitanih spojeva pokazali su snažan inhibitorni učinak na ispitivane stanične linije, što ukazuje na mogućnost njihove primjene u razvoju onkoloških lijekova