In Plenary III, @CarolynLeeMDPhD starts off with "Somatic Mutation of the OXA1L 5’UTR enables Cutaneous Squamous Cell Carcinoma". Skin cancer is the most common malignancy, and rates of SCC may be similar to BCC, 100k SCC metastasize annually with limited tx options. #SID2021 1/
Surgery is standard of care for SCC, but for many patients surgery is not an option and Dr. Lee sought to determine actionable genetic alterations in SCC to inspire targeted non-surgical treatment options #SID2021 2/n
In previous work, Dr. Lee and colleagues performed sequencing of SCC (pubmed.ncbi.nlm.nih.gov/25194279/) and did not find clear tumor driving mutations #SID2021 3/n
And in a surprise, they found that OXA1L, a gene that encodes a mitochondiral translocase, was frequently mutated in high-risk SCC. This gene is also mutated in other UV-damage induced skin cancers. #SID2021 4/n
And the plot thickens, because the mutation was not found in the exon, but instead in the 5' UTR (untranslated region). This 5' UTR location was also evident in other skin cancers from public data sets. 5/n #SID2021
Further experiments suggested that OXA1L 5'UTR mutation is functionally equivalent to loss of OXA1L. OXA1L appears to play a tumor suppressive role in the skin, and thus loss of OXA1L could drive skin tumorigenesis. 6/n #sid2021
They also tied to deduce the mechanistic implication of OXA1L loss - they found that keratinocytes with OXA1L loss were tipped metabolically to an aerobic glycosis phenotype - could this metabolic reprogramming be driving cancer? "Stay tuned!" says @CarolynLeeMDPhD 7/7 #SID2021

• • •

Missing some Tweet in this thread? You can try to force a refresh
 

Keep Current with JID Journals

JID Journals Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @JIDJournals

8 May
First State of the Art Lecture on Thursday was Isaac Brownell from the Dermatology Branch at @NIH_NIAMS, in a talk titled "Merkel cells and Merkel cell carcinoma: neuroendocrine skin cells from development to cancer" 1/n #sid2021
Merkel cells are innervated neuroendocrine cells, and they function as mechanical sensors. In mouse skin they actually cluster around specialized keratinocytes that are part of structure call the 'touch dome'
2/n #sid 2021 Image
It turns out that sonic hedgehog signaling from sensory nerves is required to maintain that touch dome - this is a deep connection between the nervous system and keratinocytes
3/n #sid2021
Read 12 tweets
7 May
Last talk of Plenary III comes from @KYTsaiLab, titled "Topical MEK Inhibition as Precision Targeted Chemoprevention". Like the 1st talk by @CarolynLeeMDPhD, this talk is focused on cutaneous squamous cell carcinoma 1/n #SID2021
In prior work (nature.com/articles/ncomm…) this group found that MEK inhibition could help prevent progression of lesions from premalignant actinic keratosis to cutaneous SCC #sid2021 2/n
They use a hairless mouse UV-driven cutaneous SCC model for preclinical testing, and found that systemic MEK inhibition prevented skin cancer lesions. To avoid systemic side effects thought, they developed a topical MEK inhibitor gel #sid2021 3/n
Read 6 tweets
7 May
Talk #3 in Plenary III - "Involucrin Deficiency results in Decreased Vitamin D Receptor‐Mediated Inflammation and Csnk1e Isoform Bias" from the lab of @cdgstrong21 at @WashUDerm #sid2021 1/n
Involucrin is a major scaffolding protein in the epidermis, and the @cdgstrong21 lab recently discovered that there is a positive selection pressure for increased involucrin expression out-of-Africa - this is work that is in press @sid2021 2/n
Interesting that involucrin knockout mice develop a normal skin barrier - but the role of involucrin for skin homeostasis is not known. To determine the response, a well known vitD agonist model of cutaneous inflammation was applied to involucrin knockout mice #sid2021 3/n
Read 8 tweets
7 May
Talk #2 from Plenary III is from @NUFeinbergDerm, José-Marc Techner, presenting "Oral Vitamin D3 reduces chemical-induced skin inflammation in humans" #SID2021 1/n
The focus of this work is to understand the mechanisms of chemical-induced skin inflammation, and to unravel how systemic vitamin D3 can suppress the deep dermal inflammatory response. @SID2021 2/n
The investigators designed a double blinded RCT - 28 healthy volunteers had 2 exposures to topical nitrogen mustard, half got vitamin D3 and half got placebo at the 2nd nitrogen mustard exposure, and labs, skin biopsy, and skin redness was measured throughout 3/n #sid2021
Read 7 tweets
7 May
"Epidemiology and risk factors for the development of cutaneous toxicities in patients treated with immune checkpoint inhibitors: A United States population-level analysis" by @EugeneSemenovMD
Immune checkpoint inhibitors have improved survival across multiple cancers. However, they can cause cutaneous immune-related adverse events (irAEs). >40 cutaneous eruptions have been associated with ICIs, including immunobullous, lichenoid dermatitis, & psoriasiform. #SID2021
They performed an observational study comparing patients on ICIs to matched controls. They found the overall incidence of immune-related adverse events to be 25% in the real world, lower than estimates in clinical trials. #SID2021
Read 6 tweets

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Too expensive? Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal Become our Patreon

Thank you for your support!

Follow Us on Twitter!

:(