Research lines
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Clinical applicability of genomic copy-number alterations and aneuploidy
Chromosomal aneuploidy results in the acquisition of copy-number alterations, which occur early in tumorigenesis and are positively selected through the lifespan of cancer cells. However, their impact in cancer development and metastasis is yet to be fully determined. A better understanding of the effect of copy-number alterations driving the adenoma-to-carcinoma transition could help better diagnose the risk of cancer progression, and improve outcomes for patients. Potentially, this could also predict what type of treatment would work better for a specific tumor. Besides chromosomal imbalances, mutational profiling by next-generation sequencing provides evidence that mutations in certain genes can also confer unique clinical outcome. Deciphering the mechanism of action of these mutated genes might provide evidence of their role in the colorectal carcinogenesis.
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Intratumor heterogeneity as a novel biomarker in colorectal cancer
Elucidating the role of genomic instability, which represents the molecular engine that fuels intratumor heterogeneity in carcinomas, is critical for our understanding of the tumor initiation, progression, and treatment response. In our group, we perform longitudinal multiregion multi-omic analyses to identify genomic alterations of cells contained within histologically areas prone to invasiveness and to decipher the spatial distribution of immune-related suppressive tumor microenvironment. Recent results suggest that subclonal distribution of genomic copy-number alterations determines disease relapse in colon cancer, thus becoming a potential biomarker of prognosis.
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Functional consequences of whole-genome doubling and its impact on disease outcome
There is growing evidence that whole-genome doubling occurs early in tumorigenesis and triggers genetically unstable near-tetraploid cells. In addition to enabling aneuploidy tolerance, our group has contributed to showing that whole-genome doubling triggers replicative stress and chromosome instability, and might also modulate the crosstalk between tumor cells and their surrounding immune infiltrate. Functional studies using in vitro 3D models will infer to what extent WGD affects metabolic pathways and define immune ‘cold’ tumors, which are less susceptible to respond to immune checkpoint blockers.