With the large number of mutations detected with duplex sequencing in normal tissue, we are approaching Natural Saturation Mutagenesis. And this allows us to compute positive selection at subgenic resolution, even per residue.

We also found a significantly increased number of TERT promoter activating mutations among smokers (ex- and current) above 55 years old.

Part of this variability is due to differences in selection between males and females, specifically on truncating mutations in RBM10, ARID1A and CDKN1A, which appear to provide stronger advantage to urothelium cells in males.

The unprecedented number of mutations per gene per sample together with the development of new analysis tools allowed us to compute the magnitude of positive selection on the mutations of each gene in each sample. This revealed a landscape of extensive interindividual variability in the cohort.

➡️ Most genes in the panel show strong signals of positive selection
➡️ Truncating mutations in FGFR3 are under negative selection
➡️ Activating mutations in the TERT promoter are under strong positive selection in normal bladder

With this approach we find thousands of somatic mutations in the normal urothelium of 45 individuals, many more than those seen in bladder tumors sequenced over two decades

Each tumor is a clone, but in normal tissue, with this approach we can detect mutations in hundreds of clones in each sample

➡️ We collected cytobrush samples from the top and the bottom of the bladder urothelium of 45 individuals during autopsy

➡️ We identified somatic mutations in 16 genes (around 5,000x) using ultra-deep error-corrected duplex sequencing

➡️ We studied clonal diversity across individuals

Human somatic tissues evolve as mosaics of competing clones driven by mutations. Most of these clones do not result in cancer, but some of them can constitute the first steps of the trajectory towards a malignant tumor. What influences this evolution in each tissue remains unknown.

European Association of Cancer Reasearch statement on threats to cancer reasearch

@helloeacr.bsky.social

eacr.org/statement-on...

#standupforscience Boston

Tackling Cancer through Global Team Science

aacrjournals.org/cancerdiscov...

Seven New Cancer Grand Challenges Announced

www.cancergrandchallenges.org/new-challenges

With awards of up to £20m ($25m). Expressions of Interest are now open.

@cancergrand.bsky.social #CancerGrandChallenges

**Clinical Cancer Genomics Conference**
First of an annual recurring series. It will be a very important meeting for the advance of clinical implementation of cancer genomics.

Proud to be part of it.

March 20th-21st 2025 in Amsterdam.

Registration open: www.ccg2025.eu
#CCG2025

Only a subset of patients respond to immunotherapy

Why? Which ones?

We conducted an unbiased analysis of response biomarkers and found that hundreds of possible biomarkers collapse into five latent, orthogonal factors that underlie immunotherapy response.

www.nature.com/articles/s41...

Work by this amazing team of scientists
@guixe-m.bsky.social
@fmuinos.bsky.social
et all not yet in this space

@bbglab.bsky.social
@irbbarcelona.bsky.social

Children who develop two independent tumors during childhood are extremely rare

We wanted to see if our genomic technologies could shed light into those exceptional cases.

Read about it in this recent paper:
tinyurl.com/yt9m584d

We recently announced a dual new release of intOGen and boostDM

Computational analysis of 33,218 tumor genomes to identify cancer genes and driver mutations

➡️ Compendium of Cancer Driver Genes - www.intogen.org

➡️ In Silico Saturation Mutagenesis of Cancer Genes - www.intogen.org/boostdm

CGI-Clinics project just joined Bluesky.

Follow it to stay tuned on exciting updates coming soon about the project

👉 @cgiclinics.bsky.social

cgiclinics.eu