Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling

• Autor(a) principal: Faldoni, Flávia L. C.
• Data de Publicação: 2020
• Outros Autores: 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., Baumbach, Jan, Marchi, Fabio A., Rogatto, Silvia R.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.3390/cancers12102816; http://hdl.handle.net/11449/206598
• topic: Copy number alterations; Gene variants; Genomic scars; Homologous recombination deficiency; Inflammatory breast cancer; Microarray

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.