RESUMO
We experienced a case of breast cancer in which liver metastases spread rapidly and the patient died of pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a fatal cancer-associated respiratory complication disease. To reveal genetic alterations of the clinical course, we performed next generation sequencing of the serial specimens using the Ion AmpliSeqTM Comprehensive Cancer Panel and RNA sequencing for transcriptomic data, followed by gene set analysis. The analysis revealed an oncogenic TP53 R213* mutation in all specimens and STK11 loss in tissues sampled after disease progression. Immunohistochemistry with an anti-STK11 antibody confirmed no STK11 expression in the samples after progression. Transcriptome analysis showed a significant downregulation of proteins associated with apoptosis in the specimens with STK11 loss. STK11 loss may have triggered the rapid progression of PTTM from a comprehensive genomic analysis.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Neoplasias Hepáticas/secundário , Microangiopatias Trombóticas/etiologia , Quinases Proteína-Quinases Ativadas por AMP , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/patologia , Evolução Fatal , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Mutação , Proteínas Serina-Treonina QuinasesRESUMO
OBJECTIVES: SMARCA4-deficient thoracic sarcoma(DTS) is a recently identified new entity of thoracic malignancies characterized by inactivation of SMARCA4. Patients with SMARCA4-DTS have a particulary aggresive clinical course and no effective treatments. However, the detailed clinical features of SMARCA4-DTS remain unclear. Here, we report the clinical courses and molecular profiles of two cases of SMARCA4-DTS. MATERIALS AND METHODS: We experienced strikingly similar two patients of SMARCA4-DTS. The clinicopathologic features were reviewed, and detailed immunohistochemical and comprehensive cancer panel analysis with next generation sequencing confirmed the diagnosis. RESULTS: Our cases had many clinical and radiological observations characteristic of SMARCA4-DTS in common. Immunohistochemical staing showed complete loss of SMARCA4 in tumor cells. Loss of function mutations were detected in SMARCA4. We found that severe SREs comprise a new significant clinical feature of SMARCA4-DTS. CONCLUSION: Integrated clinico-radiologic-pathologic-genetic diagnosis is essential for SMARCA4-DTS and physicians should pay attention to severe SREs during the clinical course of this disease.