Fusion-associated carcinomas of the breast: Diagnostic, prognostic, and therapeutic significance.
Genes Chromosomes Cancer
; 61(5): 261-273, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35106856
ABSTRACT
Recurrent gene fusions comprise a class of viable genetic targets in solid tumors that have culminated several recent breakthrough cancer therapies. Their role in breast cancer, however, remains largely underappreciated due to the complexity of genomic rearrangements in breast malignancy. Just recently, we and others have identified several recurrent gene fusions in breast cancer with important clinical and biological implications. Examples of the most significant recurrent gene fusions to date include (1) ESR1CCDC170 gene fusions in luminal B and endocrine-resistant breast cancer that exert oncogenic function via modulating the HER2/HER3/SRC Proto-Oncogene (SRC) complex, (2) ESR1 exon 6 fusions in metastatic disease that drive estrogen-independent estrogen-receptor transcriptional activity, (3) BCL2L14ETV6 fusions in a more aggressive form of the triple-negative subtype that prime epithelial-mesenchymal transition and endow paclitaxel resistance, (4) the ETV6NTRK3 fusion in secretory breast carcinoma that constitutively activates NTRK3 kinase, (5) the oncogenic MYB-NFIB fusion as a genetic driver underpinning adenoid cystic carcinomas of the breast that activates MYB Proto-Oncogene (MYB) pathway, and (6) the NOTCH/microtubule-associated serine-threonine (MAST) kinase gene fusions that activate NOTCH and MAST signaling. Importantly, these fusions are enriched in more aggressive and lethal breast cancer presentations and appear to confer therapeutic resistance. Thus, these gene fusions could be utilized as genetic biomarkers to identify patients who require more intensive treatment and surveillance. In addition, kinase fusions are currently being evaluated in breast cancer clinical trials and ongoing mechanistic investigation is exposing therapeutic vulnerabilities in patients with fusion-positive disease.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Carcinoma Adenoide Cístico
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article