Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer.
Br J Cancer
; 113(12): 1730-4, 2015 Dec 22.
Article
em 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
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aspartato Carbamoiltransferase
/
Benzamidas
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Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)
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Neoplasias Colorretais
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Rearranjo Gênico
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Receptores Proteína Tirosina Quinases
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Di-Hidro-Orotase
/
Indazóis
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Itália