Targetable ERBB2 Mutations in Neurofibroma/Schwannoma Hybrid Nerve Sheath Tumors
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ABSTRACT: Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are neoplasms associated with larger nerves that occur sporadically and in the context of schwannomatosis or neurofibromatosis (NF). Clinical management of N/S HNST is challenging, especially for large tumors, and established systemic treatments are lacking. We identified activating mutations (p.Leu755Ser, p.Asp769Tyr, p.Val777Leu) in the catalytic domain of the ERBB2 receptor tyrosine kinase in schwannomatosis-associated (4 of 8 patients) N/S HNSTs but not in tumors arising in the context of NF (0 of 6 patients), and observed that ERBB2-mutant N/S HNSTs define a distinct subgroup of peripheral nerve sheath tumors based on genome-wide DNA methylation patterns. The small-molecule ERBB inhibitor lapatinib led to prolonged clinical benefit and a lasting radiographic and metabolic response in a patient with schwannomatosis-associated, ERBB2-mutant N/S HNST. These findings uncover a key biological feature of N/S HNST that may have important diagnostic and therapeutic implications. (H021)
PROVIDER: EGAS00001003776 | EGA |
REPOSITORIES: EGA
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