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Ref Type Journal Article
PMID (27942391)
Authors Ikeda S, Goodman AM, Cohen PR, Jensen TJ, Ellison CK, Frampton G, Miller V, Patel SP, Kurzrock R
Title Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy.
Journal Vol Issue Date Pages Journal Short Title
NPJ genomic medicine 1 2016 16037- NPJ Genom Med
URL
Abstract Text Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA). The latter was performed using technology originally developed for the genome-wide detection of sub-chromosomal copy-number alterations (CNAs) in noninvasive prenatal testing and showed numerous CNAs including amplification of the 9p24.3-9p22.2 region containing PD-L1, PD-L2 and JAK2. Of interest, PD-L1, PD-L2 and JAK2 amplification is a characteristic of Hodgkin lymphoma, which is exquisitely sensitive to nivolumab. In conclusion, selected SMO antagonist-resistant metastatic basal cell carcinomas may respond to nivolumab based on underlying molecular genetic mechanisms that include PD-L1 amplification and high tumour mutational burden.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CD274 amp basal cell carcinoma predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic basal cell carcinoma harboring CD274 amplification and a high mutational burden was sensitive to treatment with Opdivo (nivolumab), demonstrating reduced lesion size after two months of treatment and a nearly complete regression of liver lesions after four months of treatment (PMID: 27942391). 27942391