Hunter Shain
@shainlab
UCSF, Department of Dermatology. Part of HTAN. Cancer, genomics, melanoma, cutaneous squamous cell carcinoma, dermatology, somatic mutations, tumor evolution, spatial transcriptomics, single-cell
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.
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 several 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. From these, we profiled 378 tumors by RNA-seq and 147 by whole-exome sequencing, balancing tumors that did and did not metastasize.
Visiting the National Cancer Institute with my colleague, Iwei Yeh, to learn about the cool science being carried out by the #HTAN project.
Celebrating 4 oral presentations from our team at the Society of Investigative Dermatology Meeting in Chicago! Loes Hollestein @sharmaharsh.bsky.social Bárbara Rentroia Pacheco and myself with support from Arne Van Hoeck and Domenico Bellomo of SkylineDx BV. Look out for new prognostic tests in cSCC
They localize to different areas within the biopsy. The copy number calls can distinguish individual tumor cells from normal cells and from different subclones
STmut clearly identified two tumor subclones, distinguished by copy number alterations on 2q, 5q, 6q, 7p, 13, and 18.
STmut can now operate on Atera data from 10X Genomics. Here is a breast cancer that was profiled on the Atera platform
@marinelab.bsky.social rocks it in the opening plenary of #AACR26, describing how to harness cellular plasticity to combat minimal residual disease. And I love the shoutout to STmut! Congrats Chris on all your success.
We have a wonderful lineup of speakers. Indu Kohaar, a Program Officer at NCI, will kick things off with an introduction to HTAN followed by scientific talks from myself, Li Ding, and Irene Ghobrial (leaders of three of the 10 HTAN centers)
I am looking forward to attending #AACR26. I will be chairing an educational session describing work done by the Human Tumor Atlas Network (HTAN) on Friday at 3pm.
On route to the Final Four. Easiest packing for a trip ever. Let’s go Illini!
Here is my haul from the American Academy of Dermatology (AAD) meeting. One of the higher yield exhibition halls of any meeting that I attend.
Keaton Wagler with the best college basketball game of the year and ESPN doesn’t even have a picture.
So what are these early mutations doing? They appear to create a mutator phenotype. Keratinocytes with TP53 or NOTCH-pathway mutations carry ~10× more mutations than nearby cells without them.
You might expect these early mutations to make cells grow faster. Surprisingly… they don’t. Mutant clones are no larger than clones without pathogenic mutations. (This echoes classic findings from Martincorena et al., Science 2015.)
What drives the earliest steps of skin cancer development? In keratinocyte cancers, the first selected mutations almost always hit TP53 and NOTCH genes—plus occasional hits in chromatin remodeling genes or the Hippo pathway.
I remain stunned by this finding -- melanocytes have 5x more mutations than keratinocytes, despite the fact that the cells are next to each other in the basal layer of the epidermis, [theoretically] experiencing the same doses of UV radiation.
Nancy Pelosi is retiring after decades of service. I still remember when I received my first R01, and she sent me a congratulatory letter!
STmut is now working on Visium HD data! Infer copy number from spatial transcriptomics data at unparalleled accuracy and resolution
Does anyone else have dogs that ruin their sleep score? I was all good till 7am, but then an intermittent Mastiff with a HrV of 300 took over
After clearly saving changes to an NIH RPPR form, the system inevitably gives this warning.