Molecular testing in metastatic basal cell carcinoma - 12/10/21
, Marlies Wakkee, MD, PhD c, Michel van Geel, PhD a, b, d, Remco van Doorn, MD, PhD e, Véronique J. Winnepenninckx, MD, PhD f, Esther Korpershoek, PhD g, Antien L. Mooyaart, MD, PhD g, An K.L. Reyners, MD, PhD h, Jorrit B. Terra, MD, PhD i, Maureen J.B. Aarts, MD, PhD b, j, Marie G.H.C. Reinders, MD, PhD a, b, Klara Mosterd, MD, PhD a, bAbstract |
Background |
Metastatic basal cell carcinoma (mBCC) is a very rare entity, and diagnosis can be challenging. Therapeutic options are limited, and response to targeted therapy is poor.
Objective |
To demonstrate a clonal relationship between BCCs and their metastases and to explore which hedgehog pathway-related mutations are involved in mBCC.
Methods |
Genetic analysis was conducted in 10 primary BCCs and their metastases. Genes relevant for BCC development were analyzed in tumor and metastasis material with small molecule molecular inversion probes (smMIPs) 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.
Results |
In 8 of 10 patients, identical gene mutations could be demonstrated in the primary tumors and their metastases. A broad spectrum of mutations was found. Four patients had SMO mutations in their tumor or metastasis, or both. All SMO mutations found were known to cause resistance to targeted therapy with vismodegib.
Limitations |
In 2 patients there was insufficient qualitative DNA available for genetic analysis.
Conclusions |
Molecular testing can help to identify the origin of a BCC metastasis and may be of prognostic and therapeutic value.
Le texte complet de cet article est disponible en PDF.Key words : basal cell carcinoma, hedgehog pathway, metastatic, molecular genetics, targeted therapy, vismodegib
Abbreviations used : BCC, Erasmus MC, FFPE, Maastricht UMC+, mBCC, NCBI, NGS, smMIP
Plan
| Funding sources: None. |
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| Conflicts of interest: Dr Aarts has advisory relationships with BMS. Drs Verkouteren, Wakkee, van Geel, van Doorn, Winnepenninckx, Korpershoek, Mooyaart, Reyners, Terra, Reinders, and Mosterd have no conflict of interest to declare. |
|
| IRB approval status: Reviewed and approved by the Maastricht University Medical Center+ Ethics Committee (#15-4-231). |
Vol 85 - N° 5
P. 1135-1142 - novembre 2021 Retour au numéro
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