| Autor: |
Andrea Remo, Federica Grillo, Luca Mastracci, Michele Simbolo, Matteo Fassan, Maria Paola Cecchini, Giuseppe Miscio, Antonio Sassano, Paola Parente, Alessandro Vanoli, Giovanna Sabella, Guido Giordano, Emanuele Damiano Urso, Luigi Cerulo, Aldo Scarpa, Francesco Fiorica, Massimo Pancione |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Genes; Volume 14; Issue 5; Pages: 984 |
| Popis: |
A rhabdoid colorectal tumor (RCT) is a rare cancer with aggressive clinical behavior. Recently, it has been recognized as a distinct disease entity, characterized by genetic alterations in the SMARCB1 and Ciliary Rootlet Coiled-Coil (CROCC). We here investigate the genetic and immunophenotypic profiling of 21 RCTs using immunohistochemistry and next-generation sequencing. Mismatch repair-deficient phenotypes were identified in 60% of RCTs. Similarly, a large proportion of cancers exhibited the combined marker phenotype (CK7-/CK20-/CDX2-) not common to classical adenocarcinoma variants. More than 70% of cases displayed aberrant activation of the mitogen-activated protein kinase (MAPK) pathway with mutations prevalently in BRAF V600E. SMARCB1/INI1 expression was normal in a large majority of lesions. In contrast, ciliogenic markers including CROCC and γ-tubulin were globally altered in tumors. Notably, CROCC and γ-tubulin were observed to colocalize in large cilia found on cancer tissues but not in normal controls. Taken together, our findings indicate that primary ciliogenesis and MAPK pathway activation contribute to the aggressiveness of RCTs and, therefore, may constitute a novel therapeutic target. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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