ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma.

Autor:	Blandin AF; Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Broad Institute of Harvard and MIT, Cambridge, Massachusetts., Giglio R; Dana-Farber Cancer Institute, Boston, Massachusetts., Graham MS; Memorial Sloan Kettering Cancer Center, New York, New York., Garcia G; Dana-Farber Cancer Institute, Boston, Massachusetts., Malinowski S; Dana-Farber Cancer Institute, Boston, Massachusetts., Woods JK; Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Broad Institute of Harvard and MIT, Cambridge, Massachusetts.; Brigham and Women's Hospital, Boston, Massachusetts., Ramkissoon S; Dana-Farber Cancer Institute, Boston, Massachusetts., Ramkissoon L; Dana-Farber Cancer Institute, Boston, Massachusetts., Dubois F; Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Broad Institute of Harvard and MIT, Cambridge, Massachusetts., Schoolcraft K; Dana-Farber Cancer Institute, Boston, Massachusetts., Tsai J; Dana-Farber Cancer Institute, Boston, Massachusetts.; Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts., Wang D; Dana-Farber Cancer Institute, Boston, Massachusetts., Jones R; Dana-Farber Cancer Institute, Boston, Massachusetts., Vogelzang J; Dana-Farber Cancer Institute, Boston, Massachusetts., Pelton K; Dana-Farber Cancer Institute, Boston, Massachusetts., Becker S; Dana-Farber Cancer Institute, Boston, Massachusetts., Watkinson F; Dana-Farber Cancer Institute, Boston, Massachusetts., Sinai C; Dana-Farber Cancer Institute, Boston, Massachusetts., Cohen EF; Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, Massachusetts., Booker MA; Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, Massachusetts., Tolstorukov MY; Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, Massachusetts., Haemels V; Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium., Goumnerova L; TromboProtea, Inc, Weston, Massachusetts., Wright K; Dana-Farber Cancer Institute, Boston, Massachusetts.; Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts., Kieran M; Day One Biopharmaceuticals, Brisbane, California., Fehnel K; Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts., Reardon D; Dana-Farber Cancer Institute, Boston, Massachusetts., Tauziede-Espariat A; GHU Paris, Sainte-Anne Hospital, Paris, France., Lulla R; Hasbro Children's Hospital, Providence, Rhode Island., Carcamo B; Texas Tech University, Health Science Center, Paul L. Foster School of Medicine, El Paso, Texas.; El Paso Children's Hospital, El Paso, Texas., Chaleff S; Maine Medical Center, Portland, Maine., Charest A; Beth Israel Deaconess Medical Center, Boston, Massachusetts., De Smet F; Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium., Ligon AH; Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Brigham and Women's Hospital, Boston, Massachusetts.; Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts., Dubuc A; Dana-Farber Cancer Institute, Boston, Massachusetts.; Brigham and Women's Hospital, Boston, Massachusetts., Pages M; Department of Genetics, Institute Curie, Paris, France.; INSERM U830, Laboratory of Translational Research in Pediatric Oncology, SIREDO Pediatric Oncology Center, Institute Curie, Paris, France., Varlet P; GHU Paris, Sainte-Anne Hospital, Paris, France., Wen PY; Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Alexander BM; Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Brigham and Women's Hospital, Boston, Massachusetts., Chi S; Dana-Farber Cancer Institute, Boston, Massachusetts.; Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts., Alexandrescu S; Dana-Farber Cancer Institute, Boston, Massachusetts.; Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts., Kittler R; University of Texas Southwestern Medical Center, Dallas, Texas., Bachoo R; University of Texas Southwestern Medical Center, Dallas, Texas., Bandopadhayay P; Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Broad Institute of Harvard and MIT, Cambridge, Massachusetts.; Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts., Beroukhim R; Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Broad Institute of Harvard and MIT, Cambridge, Massachusetts.; Brigham and Women's Hospital, Boston, Massachusetts., Ligon KL; Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Broad Institute of Harvard and MIT, Cambridge, Massachusetts.; Brigham and Women's Hospital, Boston, Massachusetts.; Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts.; Dana-Farber Cancer Institute, Center for Patient-Derived Models (CPDM), Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Jul 14; Vol. 29 (14), pp. 2651-2667.
DOI:	10.1158/1078-0432.CCR-21-3521
Abstrakt:	Purpose: Anaplastic lymphoma kinase (ALK) aberrations have been identified in pediatric-type infant gliomas, but their occurrence across age groups, functional effects, and treatment response has not been broadly established. Experimental Design: We performed a comprehensive analysis of ALK expression and genomic aberrations in both newly generated and retrospective data from 371 glioblastomas (156 adult, 205 infant/pediatric, and 10 congenital) with in vitro and in vivo validation of aberrations. Results: ALK aberrations at the protein or genomic level were detected in 12% of gliomas (45/371) in a wide age range (0-80 years). Recurrent as well as novel ALK fusions (LRRFIP1-ALK, DCTN1-ALK, PRKD3-ALK) were present in 50% (5/10) of congenital/infant, 1.4% (3/205) of pediatric, and 1.9% (3/156) of adult GBMs. ALK fusions were present as the only candidate driver in congenital/infant GBMs and were sometimes focally amplified. In contrast, adult ALK fusions co-occurred with other oncogenic drivers. No activating ALK mutations were identified in any age group. Novel and recurrent ALK rearrangements promoted STAT3 and ERK1/2 pathways and transformation in vitro and in vivo. ALK-fused GBM cellular and mouse models were responsive to ALK inhibitors, including in patient cells derived from a congenital GBM. Relevant to the treatment of infant gliomas, we showed that ALK protein appears minimally expressed in the forebrain at perinatal stages, and no gross effects on perinatal brain development were seen in pregnant mice treated with the ALK inhibitor ceritinib. Conclusions: These findings support use of brain-penetrant ALK inhibitors in clinical trials across infant, pediatric, and adult GBMs. See related commentary by Mack and Bertrand, p. 2567. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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