TY - JOUR
T1 - Molecular testing in metastatic basal cell carcinoma
AU - Verkouteren, Babette J A
AU - Wakkee, Marlies
AU - van Geel, Michel
AU - van Doorn, Remco
AU - Winnepenninckx, Véronique J
AU - Korpershoek, Esther
AU - Mooyaart, Antien L
AU - Reyners, An K L
AU - Terra, Jorrit B
AU - Aarts, Maureen J B
AU - Reinders, Marie G H C
AU - Mosterd, Klara
N1 - Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - basal cell carcinoma
KW - hedgehog pathway
KW - metastatic
KW - molecular genetics
KW - targeted therapy
KW - vismodegib
KW - GENOMIC ANALYSIS
KW - VISMODEGIB
KW - RESISTANCE
U2 - 10.1016/j.jaad.2019.12.026
DO - 10.1016/j.jaad.2019.12.026
M3 - Article
C2 - 31870915
SN - 0190-9622
VL - 85
SP - 1135
EP - 1142
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 5
ER -