Inflammatory Breast Cancer: Clinical Implications of Genomic Alterations and Mutational Profiling.

Autor: Faldoni FLC; International Research Center, A.C.Camargo Cancer Center, São Paulo 01508-010, Brazil.; Department of Clinical Genetics, University Hospital of Southern Denmark, 7100 Vejle, Denmark., Villacis RAR; Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília-UnB, Brasília 70910-900, Brazil., Canto LM; Department of Clinical Genetics, University Hospital of Southern Denmark, 7100 Vejle, Denmark., Fonseca-Alves CE; Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University-UNESP, Botucatu 18618-681, Brazil., Cury SS; Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University-UNESP, Botucatu 18618-689, Brazil., Larsen SJ; Department of Mathematics and Computer Science, University of Southern Denmark, 5230 Odense, Denmark., Aagaard MM; Department of Clinical Genetics, University Hospital of Southern Denmark, 7100 Vejle, Denmark., Souza CP; Department of Breast and Gynecologic Oncology, Barretos Cancer Hospital, Pio XII Foundation, Barretos 14784-390, Brazil., Scapulatempo-Neto C; Molecular Oncology Research Center, Barretos, SP, 14784-400, and Diagnósticos da América (DASA), Barueri 01525-001, Brazil., Osório CABT; Department of Pathology, A.C.Camargo Cancer Center, São Paulo 01525-001, Brazil., Baumbach J; Department of Mathematics and Computer Science, University of Southern Denmark, 5230 Odense, Denmark.; TUM School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany., Marchi FA; International Research Center, A.C.Camargo Cancer Center, São Paulo 01508-010, Brazil., Rogatto SR; Department of Clinical Genetics, University Hospital of Southern Denmark, 7100 Vejle, Denmark.; Institute of Regional Health Research, University of Southern Denmark, 500 Odense, Denmark.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2020 Sep 30; Vol. 12 (10). Date of Electronic Publication: 2020 Sep 30.
DOI: 10.3390/cancers12102816
Abstrakt: 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.
Databáze: MEDLINE
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