NUT midline carcinoma (NMC) is a rare and aggressive epithelial cancer arising from median organs. It is driven by chromosomal translocation t(15;19) involving the rearrangement of NUT (nuclear protein in testis) and BRD4 (bromodomain 4) genes leading to fusion oncoprotein BRD4-NUT.
We report the case of a woman who was previously treated with induction chemotherapy, surgery, radiotherapy and adjuvant trastuzumab for HER-2 positive invasive ductal carcinoma of the breast. After 6 months of follow-up a lung nodule appeared. A biopsy showed an adenocarcinoma fetal type/lung blastoma, so a left inferior lobectomy was performed: NMC harboring BRD4-NUT rearrangement was diagnosed. After 9 months of follow-up, bone and soft tissue metastases occurred, so the patient was given radiotherapy. Next-generation sequencing technology identified somatic mutations in deleted in colorectal cancer (DCC), mixed lineage leukemia protein 3 (MLL3), and splicing factor 3B subunit 1 (SF3B1) genes in NMC cells from both primitive cancer and metastases. The patient was treated with the experimental BRD4 inhibitor for 10 months, until the disease progressed to the lung and bone. After spinal cord compression, the patient was offered palliative radiotherapy to bone and eventually died aged 39 years.
To the best of our knowledge, our case is the first DCC, MLL3, and SF3B1 mutated NUT midline carcinoma reported in the literature. If these mutations were confirmed to play a role in this neoplasm, clinical trials analyzing targeted therapies should be considered, eg. colorectal cancer-like chemotherapies for DCC mutations, hypomethylating agents for MLL3 mutations or SF3B1 inhibitors in case of specific somatic mutations.
Post author correction
Article Type: CASE REPORT
AuthorsStefano Cavalieri, Anastasios Stathis, Alessandra Fabbri, Angelica Sonzogni, Federica Perrone, Elena Tamborini, Giuseppe Pelosi, Filippo de Braud, Marco Platania
- • Accepted on 13/09/2017
- • Available online on 25/09/2017
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- Cavalieri, Stefano [PubMed] [Google Scholar] 1, * Corresponding Author (firstname.lastname@example.org)
- Stathis, Anastasios [PubMed] [Google Scholar] 2
- Fabbri, Alessandra [PubMed] [Google Scholar] 3
- Sonzogni, Angelica [PubMed] [Google Scholar] 3
- Perrone, Federica [PubMed] [Google Scholar] 3
- Tamborini, Elena [PubMed] [Google Scholar] 3
- Pelosi, Giuseppe [PubMed] [Google Scholar] 3
- de Braud, Filippo [PubMed] [Google Scholar] 1, 4
- Platania, Marco [PubMed] [Google Scholar] 1
Medical Oncology Department, IRCCS Fondazione Istituto Nazionale dei Tumori, Milan - Italy
Istituto Oncologico della Svizzera Italiana, Ente Ospedaliero Cantonale, Bellinzona - Switzerland
Pathology Department, IRCCS Fondazione Istituto Nazionale dei Tumori, Milan - Italy
Medical Oncology Department, University of Milan, Milan - Italy