Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling
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Data
2020-10-01
Autores
Faldoni, Flávia L. C.
Villacis, Rolando A. R.
Canto, Luisa M.
Fonseca-Alves, Carlos E. [UNESP]
Cury, Sarah S. [UNESP]
Larsen, Simon J.
Aagaard, Mads M.
Souza, Cristiano P.
Scapulatempo-Neto, Cristovam
Osório, Cynthia A. B. T.
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Resumo
Inflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer whose molecular basis is poorly understood. We performed a comprehensive molecular analysis of 24 IBC biopsies naïve of treatment, using a high-resolution microarray platform and targeted next-generation sequencing (105 cancer-related genes). The genes more frequently affected by gains were MYC (75%) and MDM4 (71%), while frequent losses encompassed TP53 (71%) and RB1 (58%). Increased MYC and MDM4 protein expression levels were detected in 18 cases. These genes have been related to IBC aggressiveness, and MDM4 is a potential therapeutic target in IBC. Functional enrichment analysis revealed genes associated with inflammatory regulation and immune response. High homologous recombination (HR) deficiency scores were detected in triple-negative and metastatic IBC cases. A high telomeric allelic imbalance score was found in patients having worse overall survival (OS). The mutational profiling was compared with non-IBC (TCGA, n = 250) and IBC (n = 118) from four datasets, validating our findings. Higher frequency of TP53 and BRCA2 variants were detected compared to non-IBC, while PIKC3A showed similar frequency. Variants in mismatch repair and HR genes were associated with worse OS. Our study provided a framework for improved diagnosis and therapeutic alternatives for this aggressive tumor type.
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Copy number alterations, Gene variants, Genomic scars, Homologous recombination deficiency, Inflammatory breast cancer, Microarray
Como citar
Cancers, v. 12, n. 10, p. 1-21, 2020.