Publications by authors named "Sara Ruiz Gil"
The interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a cohort of metastatic triple-negative breast cancers. We demonstrate that a continuous increase in tumor genomic heterogeneity and distinct molecular clocks correlated with resistance to treatment, eventually allowing tumors to escape from immune control.
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- Richter transformation (RT) is a severe progression of chronic lymphocytic leukemia (CLL) into aggressive large B cell lymphoma with poor outcomes.
- Researchers analyzed the genome and transcriptome of 19 CLL cases that developed RT, studying samples over nearly two decades to detect early subclones associated with RT features.
- They found new genetic drivers and a specific mutational signature for RT, as well as identified a pathway that could be targeted for therapy by inhibiting oxidative phosphorylation in RT cells.
Fatty acid uptake and altered metabolism constitute hallmarks of metastasis, yet evidence of the underlying biology, as well as whether all dietary fatty acids are prometastatic, is lacking. Here we show that dietary palmitic acid (PA), but not oleic acid or linoleic acid, promotes metastasis in oral carcinomas and melanoma in mice. Tumours from mice that were fed a short-term palm-oil-rich diet (PA), or tumour cells that were briefly exposed to PA in vitro, remained highly metastatic even after being serially transplanted (without further exposure to high levels of PA).
View Article and Find Full Text PDFCD4 and CD8 mark helper and cytotoxic T cell lineages, respectively, and serve as coreceptors for MHC-restricted TCR recognition. How coreceptor expression is matched with TCR specificity is central to understanding CD4/CD8 lineage choice, but visualising coreceptor gene activity in individual selection intermediates has been technically challenging. It therefore remains unclear whether the sequence of coreceptor gene expression in selection intermediates follows a stereotypic pattern, or is responsive to signaling.
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- - The study focuses on the NIPBL/MAU2 complex, which is crucial for loading cohesin onto chromatin, and how mutations in NIPBL are linked to Cornelia de Lange syndrome (CdLS).
- - A specific MAU2 variant causing CdLS was identified, which disrupts its interaction with NIPBL, yet other findings showed that cell lines can function normally despite having this mutation.
- - The research indicates that cohesin loading can occur without the typical NIPBL/MAU2 interaction, suggesting an alternative mechanism that may help protect against serious genetic mutations and could inform understanding of various genetic disorders.
Article Synopsis
- Cornelia de Lange syndrome (CdLS) is a genetic developmental disorder caused by mutations in specific genes, primarily affecting the cohesin complex, with NIPBL being the most significant gene involved.
- Many mutations in CdLS patients are found to be somatic mosaicism, meaning they can vary in different tissues and often go unnoticed in standard tests using blood DNA.
- This study highlights the importance of advanced sequencing methods in detecting low-level mosaicism for accurate diagnosis and genetic counseling in CdLS cases, reporting two patients with atypical manifestations and challenges in identifying mutations.
The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex.
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