Targeted RNA sequencing of head and neck adenoid cystic carcinoma reveals SEC16A::NOTCH1 fusion and MET exon 14 skipping as potentially actionable alterations Journal Article
| Authors: | Chu, Y. H.; Xu, B.; Sukhadia, P.; Mohanty, A. S.; DiNapoli, S. E.; Ho, A. L.; Katabi, N.; Dogan, S. |
| Article Title: | Targeted RNA sequencing of head and neck adenoid cystic carcinoma reveals SEC16A::NOTCH1 fusion and MET exon 14 skipping as potentially actionable alterations |
| Abstract: | Purpose: Adenoid cystic carcinoma (AdCC) of the head and neck harbors MYB/MYBL1::NFIB fusions in around 60% of cases, with unfavorable long-term survival due to frequent recurrences and metastases, currently lacking effective targeted therapy. The study aims to identify actionable alterations and to elucidate the molecular underpinnings of MYB/MYBL1::NFIB-negative AdCC using a large targeted RNA sequencing panel. Methods and Results: We retrospectively searched our MSK-Solid Fusion clinical sequencing database for head and neck AdCC sequenced between 2016 and 2023. Of a total of 55 cases, 28 showed MYB::NFIB, 7 showed MYBL1::NFIB, and one case each harbored MYB::MPDZ (case 1) and FUS::MYB (case 2). One base of tongue tumor expressed both MYB::NFIB fusion and MET exon 14 skipping transcripts due to concurrent MET splice site mutation, D1010N (case 3). One parotid tumor lacked MYB/MYBL1 rearrangement but instead showed an in-frame SEC16A::NOTCH1 fusion that preserved the secretase cleavage site (case 4). Clinical records on 4 cases with non-canonical sequencing findings were reviewed. Distant metastases were present at the initial diagnosis (case 2) or at recurrence (cases 1, 3, and 4). Disease-related mortality occurred in cases 2 and 4 despite radiotherapy and immunotherapy. Conclusions: The study improved the understanding of AdCC providing the first documentation of tumor clinical behavior associated with MYB::MPDZ and FUS::MYB fusions and reporting potentially actionable SEC16A::NOTCH1 fusion and MET exon 14 skipping mutation. Further research is needed to explore the therapeutic utility of MET inhibition and the efficacy of γ-secretase inhibitors against rare NOTCH1 fusions in AdCC. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. |
| Keywords: | adult; aged; middle aged; retrospective studies; exon; genetics; exons; receptor, notch1; pathology; retrospective study; head and neck neoplasms; gene fusion; oncogene proteins, fusion; adenoid cystic carcinoma; sequence analysis, rna; carcinoma, adenoid cystic; head and neck tumor; notch1 receptor; scatter factor receptor; met; proto-oncogene proteins c-met; notch1; notch1 protein, human; met protein, human; humans; human; male; female; fus; rna sequencing; oncogene fusion protein; oncogenic isoform |
| Journal Title: | Head and Neck Pathology |
| Volume: | 18 |
| ISSN: | 1936-055X |
| Publisher: | Humana Press Inc |
| Date Published: | 2024-11-07 |
| Start Page: | 119 |
| Language: | English |
| DOI: | 10.1007/s12105-024-01694-7 |
| PUBMED: | 39508931 |
| PROVIDER: | scopus |
| PMCID: | PMC11543961 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Snjezana Dogan -- Source: Scopus |
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