Background: Using array comparative genomic hybridization (aCGH), a large number of deleted genomic regions have been identified in human cancers. However, subsequent efforts to identify target genes selected for inactivation in these regions have often been challenging.
Methods: We integrated here genome-wide copy number data with gene expression data and non-sense mediated mRNA decay rates in breast cancer cell lines to prioritize gene candidates that are likely to be tumour suppressor genes inactivated by bi-allelic genetic events. The candidates were sequenced to identify potential mutations.
Results: This integrated genomic approach led to the identification of RIC8A at 11p15 as a putative candidate target gene for the genomic deletion in the ZR-75-1 breast cancer cell line. We identified a truncating mutation in this cell line, leading to loss of expression and rapid decay of the transcript. We screened 127 breast cancers for RIC8A mutations, but did not find any pathogenic mutations. No promoter hypermethylation in these tumours was detected either. However, analysis of gene expression data from breast tumours identified a small group of aggressive tumours that displayed low levels of RIC8A transcripts. qRT-PCR analysis of 38 breast tumours showed a strong association between low RIC8A expression and the presence of TP53 mutations (P = 0.006).
Conclusion: We demonstrate a data integration strategy leading to the identification of RIC8A as a gene undergoing a classical double-hit genetic inactivation in a breast cancer cell line, as well as in vivo evidence of loss of RIC8A expression in a subgroup of aggressive TP53 mutant breast cancers.
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http://dx.doi.org/10.1186/1755-8794-2-26 | DOI Listing |
J Clin Oncol
January 2025
German Breast Group, Neu-Isenburg, Germany.
Purpose: To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC).
Methods: Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points.
Breast and cervical cancers are the most prevalent diagnosed in women worldwide, significantly contributing to maternal morbidity and mortality. We examined socio-demographic and behavioral factors associated with breast and cervical cancer screening among Cambodian women aged 15-49 years old. We analyzed women's data from the 2022 Cambodia Demographic and Health Survey (CDHS).
View Article and Find Full Text PDFJNCI Cancer Spectr
January 2025
Division of Cardiology, Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GA, United States.
Background: Cancer patients have up to a 3-fold higher risk for cardiovascular disease (CVD) than the general population. Traditional CVD risk scores may be less accurate for them. We aimed to develop cancer-specific CVD risk scores and compare them with conventional scores in predicting 10-year CVD risk for patients with breast cancer (BC), colorectal cancer (CRC), or lung cancer (LC).
View Article and Find Full Text PDFACS Biomater Sci Eng
January 2025
Nano 2 Micro Material Design Lab, Department of Chemical Engineering and Technology, IIT (BHU), Varanasi 221005, India.
Herein, fluorescent calcium carbonate nanoclusters encapsulated with methotrexate (Mtx) and surface functionalized with chitosan (25 nm) (@Calmat) have been developed for the imaging and treatment of triple-negative breast cancer (TNBC). These biocompatible, pH-sensitive nanoparticles demonstrate significant potential for targeted therapy and diagnostic applications. The efficacy of nanoparticles (NPs) was evaluated in MDA-MB-231 TNBC cell lines.
View Article and Find Full Text PDFDalton Trans
January 2025
CEQUINOR (UNLP, CCT-CONICET La Plata, asociado a CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Blvd. 120 No. 1465, La Plata (1900), Argentina.
In this work, we evaluated the anticancer activity of compounds 1 (mononuclear) and 2 (dinuclear) copper(II) coordination compounds derived from the ligand 5-methylsalicylaldehyde 2-furoyl hydrazone (H2L) over MDA-MB-231 Triple-negative breast cancer (TNBC) cells, and compared their activities with that of a newly synthesized, protonated, dinuclear analogue of 2 (complex 3). Here, we report the synthesis of compound 3 and it has been characterized in the solid state (X-ray diffraction, FTIR) and in solution (EPR, UV-Vis, ESI) as well as its electrochemical profile. Complexes 1-3 impaired cell viability from 0.
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