My 100lb dog and I are tag teaming the @eightsleep app. Got an extra daytime sleep session in from 8am to 5pm, bringing our surplus sleep to nearly 25 hrs!

I have not seen the data, but investors have. All signs suggest that the mRNA vaccine works in a phase III clinical trial.

Importantly, SCCore-GEP performed well on biopsy material. That creates the possibility of estimating metastatic risk before definitive excision—when the result could help guide surgical planning, imaging, follow-up and consideration of (neo)adjuvant therapy.

SCCore-GEP was validated in 2 independent cohorts, where it outperformed staging systems and provided prognostic information independent of clinical models.

We distilled these transcriptional programs into SCCore-GEP: a 23-gene signature that largely measures tumor differentiation, with additional contributions from normal epithelial, stromal and immune cells.

Gene expression told an especially clear story. Tumors formed differentiated, basal-like and mesenchymal-like groups with progressively worse metastasis-free survival. Differentiation state—not immune programs—was the dominant axis separating outcomes.

A key strength of this study is that we have outcome information on each tumor. Poor outcome was associated with alterations in SWI/SNF, RAS–MAPK/PI3K and TGF-β pathways, as well as arm-level copy-number changes. These features reveal genetic routes to metastatic competence.

We identified 38 driver genes converging on a core set of pathways. This was NOT easy because of the high mutation burden in these tumors. This is IMHO the cleanest and most curated list of driver genes in this cancer subtype to date

The mutational landscape was dominated by UV radiation, with additional contributions from aging, APOBEC activity and—in immunosuppressed patients—azathioprine exposure.

We started by assembling the D-SQUAME study: a nationwide Dutch cohort of 19,120 patients with detailed clinicopathologic annotation and long-term outcomes. We profiled 378 tumors by RNA-seq and 147 by whole-exome sequencing, balancing tumors that did and did not metastasize.

Major preprint from our group is out. Looking for feedback. We built the largest molecular atlas of cutaneous squamous cell carcinoma (cSCC) to date linking somatic mutations and gene expression patterns to metastatic outcome. A Thread 🧵