Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer.
Br J Cancer
; 113(12): 1730-4, 2015 Dec 22.
Article
en En
| MEDLINE
| ID: mdl-26633560
ABSTRACT
BACKGROUND:
Activated anaplastic lymphoma kinase (ALK) gene fusions are recurrent events in a small fraction of colorectal cancers (CRCs), although these events have not yet been exploited as in other malignancies.METHODS:
We detected ALK protein expression by immunohistochemistry and gene rearrangements by fluorescence in situ hybridisation in the ALKA-372-001 phase I study of the pan-Trk, ROS1, and ALK inhibitor entrectinib. One out of 487 CRCs showed ALK positivity with a peculiar pattern that prompted further characterisation by targeted sequencing using anchored multiplex PCR.RESULTS:
A novel ALK fusion with the carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) gene (CAD-ALK fusion gene) was identified. It resulted from inversion within chromosome 2 and the fusion of exons 1-35 of CAD with exons 20-29 of ALK. After failure of previous standard therapies, treatment of this patient with the ALK inhibitor entrectinib resulted in a durable objective tumour response.CONCLUSIONS:
We describe the novel CAD-ALK rearrangement as an oncogene and provide the first evidence of its drugability as a new molecular target in CRC.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Aspartato Carbamoiltransferasa
/
Benzamidas
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Carbamoil-Fosfato Sintasa (Glutamina-Hidrolizante)
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Neoplasias Colorrectales
/
Reordenamiento Génico
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Proteínas Tirosina Quinasas Receptoras
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Dihidroorotasa
/
Indazoles
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Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Año:
2015
Tipo del documento:
Article
País de afiliación:
Italia