Abstract*

Purpose
Aggressive cutaneous squamous cell carcinoma (cSCC) is often a disfiguring and lethal disease. Very little is currently known about the mutations that drive aggressive cSCC.

Experimental Design
Whole exome sequencing was performed on 39 cases of aggressive cSCC to identify driver genes and novel therapeutic targets. 

Significantly mutated genes were identified with MutSig or complementary methods developed to specifically identify candidate tumor suppressors based upon their inactivating mutation bias.

Results
Despite the very high mutational background caused by UV exposure, 23 candidate drivers were identified including the well-known cancer-associated genes TP53, CDKN2A, NOTCH1, AJUBA, HRAS, CASP8, FAT1, and KMT2C (MLL3)

Three novel candidate tumor suppressors with putative links to cancer or differentiation, NOTCH2, PARD3 and RASA1, were also identified as possible drivers in cSCC. KMT2C mutations were associated with poor outcome and increased bone invasion.

Conclusions
The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor suppressor genes. 

These results improve the foundation for understanding this disease and should aid in identifying and treating aggressive cSCC.
 
Keywords
Head and neck/oral cancers; Melanoma/skin cancers; Mutagenesis; Oncogenes; Suppressor genes; Somatic alterations and genetic and environmental risk factors; cutaneous squamous cell carcinoma; cSCC; genomics

The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor suppressor genes. 



*Texto retirado na íntegra da seção abstract da referência 1.


Quer conferir o artigo na íntegra? Solicite para o e-mail marcela.frota@sanofi.com.