Molecular testing helps pinpoint origin of BCC metastasis

Molecular testing may be used to identify the origin of a basal cell carcinoma (BCC) metastasis, indicating its prognostic and therapeutic value, suggests a recent study.

“Metastatic BCC is a very rare entity, and diagnosis can be challenging,” the authors said. “Therapeutic options are limited, and response to targeted therapy is poor.”

This study sought to determine a clonal relationship between BCCs and their metastases, as well as to explore which hedgehog pathway-related mutations were involved in metastatic BCC. A genetic analysis was carried out in 10 primary BCCs and their metastases.

The authors then analysed genes relevant for BCC development in tumour and metastasis material with small molecule molecular inversion probes for PTCH1, PTCH2, SMO, SUFU, GLI2, and TP53 or with targeted next-generation sequencing of the same genes and CDKN2A, CDKN2B, CIC, DAXX, DDX3X, FUBP1, NF1, NF2, PTEN, SETD2, TRAF7, and the TERT promoter.

Molecular testing showed that identical gene mutations could be exhibited in the primary tumours and their metastases in eight of 10 patients. In addition, a broad spectrum of mutations was discovered. Four patients had SMO mutations in their tumour or metastasis, or both.

“All SMO mutations found were known to cause resistance to targeted therapy with vismodegib,” the authors said.

The study was limited by insufficient qualitative DNA available for genetic analysis in two patients.