Widely metastatic glioblastoma with BRCA1 and ARID1A mutations: a case report
| العنوان: | Widely metastatic glioblastoma with BRCA1 and ARID1A mutations: a case report |
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| المؤلفون: | Melissa Umphlett, Mary Fowkes, Stephanie Shea, Raymund Yong, Jessica Tome-Garcia, Yizhou Zhang, Nadejda M. Tsankova, Adilia Hormigo |
| المصدر: | BMC Cancer, Vol 20, Iss 1, Pp 1-8 (2020) BMC Cancer |
| بيانات النشر: | BMC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Malignant Brain Neoplasm, Cancer Research, Pathology, DNA Mutational Analysis, Case Report, Autopsy, Treatment resistance, Mice, SCID, DNA Mismatch Repair, Metastasis, Mice, 0302 clinical medicine, Surgical oncology, Tumor Cells, Cultured, Medicine, Neoplasm Metastasis, BRCA1 Protein, Brain Neoplasms, ARID1A mutation, Debulking, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Primary tumor, 3. Good health, DNA-Binding Proteins, Oncology, 030220 oncology & carcinogenesis, Female, medicine.drug, medicine.medical_specialty, Radiosurgery, lcsh:RC254-282, 03 medical and health sciences, Germline mutation, BRCA1 mutation, Genetics, Temozolomide, Animals, Humans, Antineoplastic Agents, Alkylating, Aged, business.industry, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Mutation, Neoplasm Recurrence, Local, business, Glioblastoma, Mismatch repair deficiency, Transcription Factors |
| الوصف: | Background Glioblastoma (GBM) is a highly malignant brain neoplasm with poor survival. Despite its aggressive nature, metastatic spread of GBM is identified only rarely. While the molecular alterations associated with GBM and its subtypes are well-described, there remains a gap in understanding which alterations may predispose towards metastasis. In this report, we present a case of GBM with multi-organ metastases and discuss its genomic alterations. Case presentation A 74-year-old woman was diagnosed with left occipital glioblastoma (IDH-wildtype, MGMT-unmethylated), for which she underwent resection, standard chemoradiation, and then stereotactic radiosurgery (SRS) for local recurrence. One month after SRS, work-up for a pathologic hip fracture revealed a left breast mass, lytic lesions involving pelvic bones, and multiple pulmonary and hepatic lesions. Biopsies of the breast and bone lesions both demonstrated metastatic IDH-wildtype GBM. For worsening neurologic symptoms, the patient underwent debulking of a large right temporal lobe recurrence and expired shortly thereafter. Autopsy confirmed metastatic GBM in multiple systemic sites, including bilateral lungs, heart, liver, thyroid, left breast, small bowel, omentum, peritoneal surfaces, visceral surfaces, left pelvic bone, and hilar lymph nodes. Targeted sequencing was performed on tissue samples obtained pre- and postmortem, as well as on cell cultures and an orthotopic mouse xenograft derived from premortem surgical specimens. A BRCA1 mutation (p.I571T) was the only variant found in common among the primary, recurrence, and metastatic specimens, suggesting its likely status as an early driver mutation. Multiple subclonal ARID1A mutations, which promote genomic instability through impairment of DNA mismatch repair, were identified only in the recurrence. Mutational spectrum analysis demonstrated a high percentage of C:G to T:A transitions in the post-treatment samples but not in the primary tumor. Conclusion This case report examines a rare case of widely metastatic IDH-wildtype GBM with a clonal somatic mutation in BRCA1. Post-treatment recurrent tumor in the brain and in multiple systemic organs exhibited evidence of acquired DNA mismatch repair deficiency, which may be explained by functional loss of ARID1A. We identify a potential role for immune checkpoint and PARP inhibitors in the treatment of metastatic GBM. |
| اللغة: | English |
| تدمد: | 1471-2407 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b90e04569eadb657cc30d713e3120aaTest https://doaj.org/article/55a688632fdb4857adb89bd21cccb2a8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1b90e04569eadb657cc30d713e3120aa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712407 |
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