Thread by @JIDJournals

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