Case Report: Structurally Rare EML4-ALK Identified by Next Generation Sequencing in a Patient with NSCLC with Bilateral Ovarian Metastases.

Autor: Maruta R; Department of Respiratory Medicine, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Japan.; Department of Respiratory Medicine, Tokyo Metropolitan Bokutoh Hospital, Sumida-ku, Japan., Sadato D; Clinical Research Support Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Japan., Yomota M; Department of Respiratory Medicine, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Japan., Gomikawa R; Department of Pathology, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Japan., Motoi T; Department of Pathology, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Japan., Sato T; Department of Gynecology, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Japan., Kino N; Department of Gynecology, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Japan., Kobayashi M; Department of Respiratory Medicine, Tokyo Metropolitan Bokutoh Hospital, Sumida-ku, Japan., Hosomi Y; Department of Respiratory Medicine, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Japan.
Jazyk: angličtina
Zdroj: OncoTargets and therapy [Onco Targets Ther] 2024 Sep 23; Vol. 17, pp. 777-783. Date of Electronic Publication: 2024 Sep 23 (Print Publication: 2024).
DOI: 10.2147/OTT.S474134
Abstrakt: The EML4-ALK oncogene is a fusion of the EML4 and ALK genes and is found in approximately 5-6% of the cases of non-small cell lung cancer (NSCLC). Herein, we present a unique case of lung adenocarcinoma with metastases to the bilateral ovaries harboring a rare EML4-ALK fusion gene variant in a 52-year-old patient. The patient had initially received a diagnosis of ovarian cancer, then had undergone neo-adjuvant chemotherapy followed by a surgical resection. Despite two cycles of adjuvant chemotherapy consisting of carboplatin and gemcitabine, CT revealed that the pleural effusion had increased from it before chemotherapy, and the shortness of breath worsened. Molecular profiling revealed an EML4-ALK rearrangement containing ALK -EML4 and ALK -NPR2 fusion genes. The diagnosis was changed to primary lung adenocarcinoma with metastases to the bilateral ovaries based on a pathological reevaluation. Treatment with alectinib, a second-generation ALK-tyrosine kinase inhibitor, led to a partial response of 18 months' duration, and the shortness of breath improved. No adverse events related to the alectinib therapy occurred. To assess the unique structure of the fusion genes, RNA sequencing was performed. An intronic sequence from both ALK and EML4 was found between ALK and EML4 exon, possibly because of an unusual insertion of a gene fragment derived from NRP2 , indicated by the panel sequencing results. Variations in the drug response among EML4-ALK fusion variants highlight the importance of understanding their molecular structure. Further investigation is warranted to refine fusion gene detection methods and assess the therapeutic implications of rare fusion variants.
Competing Interests: M.Y. received honoraria (lecture fee) from AstraZeneca, Takeda, MSD, Chugai Pharmaceutical, Ono Pharmaceutical, and Bristol-Myers Squibb. M.K. received honoraria (lecture fee) from AstraZeneca and Chugai Pharmaceutical. Y. H. received honoraria (lecture fee) from AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Nippon Kayaku, Takeda, Eisai, Novartis, Pfizer and MSD. The other authors declare that they have no conflicts of interest.
(© 2024 Maruta et al.)
Databáze: MEDLINE
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