Francisco Gimeno-Valiente

What an amazing friend to be proud of! You did it, Noe! Such an incredible recognition from the scientific community, so well deserved. Everyone in your group loves you!!! 💖💖 Thank you for everything!

Amazing session at @ASEICAnews 2025 on resistance to anticancer therapy, chaired by @TarazonaNoelia and @pedrofsrocha 🔬🧬

🚨The SERENA-6 trial shows that acting before radiologic progression can matter. Switching to camizestrant upon emerging ESR1 mutations in ctDNA🩸extended PFS and delayed QoL decline in HR+/HER2-BC. 👟A step closer to real-time, biology-driven care. ✍️@OrtegaTolosa @evaciruelos

Great lecture by Nnenna Kannu @ucl at @myESMO MAP2025 featuring the DNA #methylation patterns of the amazing #lungcancer TRACERx cohort, now at @NatureGenet ! Congrats to @CharlesSwanton and @MariamJHanjani, too!

🚀 Hoy hemos celebrado la reunión de inicio del proyecto #MOLECULAR, dirigido a mejorar el abordaje del cáncer de cabeza y cuello localmente avanzado mediante el análisis del ADN tumoral en sangre e IA. 👩‍🔬 Esta iniciativa colaborativa está coordinada por la Dra. Gema Bruixola.

(13/13) Thank you to the patients and their families, without which we would not be able to start this project. Thank you to all our funders without which our work would not be possible @thecrick @crukcolcentre @cr_UK @uclcancer @rosetreest

(12/13) This work would not be possible without @miljana_21, @zeunas, @stephanbeck6

(11/13) Validation in an independent cohort confirms MRMN’s predictive power: Sensitivity: 80.7% Specificity: 83.3% Strong evidence that epigenomic drivers act as critical cooperators in NSCLC evolution.

(10/13) Genes with positive MRMN associate with cancer development pathways & poor DFS. Essential genes have significantly lower MRMNvalues.

(9/13) AllChAT is enriched in essential genes and methylation-based driver genes. We introduce MRMN to further stratify methylation-based driver genes

(8/13) We define a mechanism: AllChAT (Allosteric Chromatin Activity Transition). CN changes induce chromatin compaction neighbouring oncogenes → fostering local passenger hypermethylation.

(7/13) This methylation-driven compensation arises in amplicons containing oncogenes. Oncogenes scale expression with amplification, while neighboring dosage-compensated genes are enriched for essential genes.

(6/13) Conversely, we also observe hypermethylation co-occurring with CN amplification, leading to dosage compensation effect on gene expression on autosomal genes.

(5/13) We investigated the temporal order of alterations: Epigenomic cancer genes:methylation typically precedes CN loss. Genomic TSGs: CN loss often occurs first, followed by methylation.

(4/13) This correlation suggests that epigenomic + genomic cooperation jointly drives NSCLC evolution. TSGs can be inactivated by single drivers, two drivers, or parallel evolutionary trajectories.

(3/13) We developed a novel metric of intratumor methylation distance: I-TMD. I-TMD correlates positively with SNV-based ITH, SCNA-based ITH, and ITED, reinforcing the link between epigenomic and genomic heterogeneity.

(2/13) We applied CAMDAC, a deconvolution method, to extract RRBS-based methylation signals free from confounding copy-number effects and contamination from non-tumor cells.

Proud to share our first TRACERx cancer study integrating epigenomics + genomics in NSCLC as co-drivers of tumor evolution. Led by not me but by the wonderful @NnennayaKanu, @F_gimenoval, @ccastignani6, @VanLooLab

and the cover of the September issue! 🔥

🔥New in @NatureGenet by @F_gimenoval during his postdoc at @ucl under @NnennayaKanu @CharlesSwanton 🔝 📌Genomic & epigenomic drivers converge in lung cancer. New methylation dN/dS + AllChAT reveal chromatin-driven dosage compensation. 🔗nature.com/articles/s4158…