Analysis of the Genomic Landscape in ALK+ NSCLC Patients Identifies Novel Aberrations Associated with Clinical Outcomes.

Autor:	Couëtoux du Tertre M; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.; Exactis Innovation, Montreal, Quebec, Canada., Marques M; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.; Exactis Innovation, Montreal, Quebec, Canada., Tremblay L; Institut Universitaire de Cardiologie et Pneumologie de Quebec, Universite de Laval, Quebec City, Quebec, Canada., Bouchard N; Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada., Diaconescu R; Hopital Sacre Cœur Montreal, Montreal, Quebec, Canada., Blais N; Centre Hospitalier Universitaire de Montreal, Montreal, Quebec, Canada., Couture C; Institut Universitaire de Cardiologie et Pneumologie de Quebec, Universite de Laval, Quebec City, Quebec, Canada., Pelsser V; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada., Wang H; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada., Higenell V; Exactis Innovation, Montreal, Quebec, Canada., Izzi L; Exactis Innovation, Montreal, Quebec, Canada., Gambaro K; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.; Exactis Innovation, Montreal, Quebec, Canada., Hoffert C; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.; Exactis Innovation, Montreal, Quebec, Canada., Srivastava A; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.; Exactis Innovation, Montreal, Quebec, Canada., Spatz A; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada., Rousseau C; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada., McNamara S; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.; Exactis Innovation, Montreal, Quebec, Canada., Cohen V; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada., Batist G; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. gerald.batist@mcgill.ca jagulnik@jgh.mcgill.ca., Agulnik J; Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. gerald.batist@mcgill.ca jagulnik@jgh.mcgill.ca.
Jazyk:	angličtina
Zdroj:	Molecular cancer therapeutics [Mol Cancer Ther] 2019 Sep; Vol. 18 (9), pp. 1628-1636. Date of Electronic Publication: 2019 Jun 26.
DOI:	10.1158/1535-7163.MCT-19-0105
Abstrakt:	Rearrangements in the anaplastic lymphoma kinase ( ALK ) gene are found in approximately 5% of non-small cell lung carcinoma (NSCLC). Here, we present a comprehensive genomic landscape of 11 patients with ALK+ NSCLC and investigate its relationship with response to crizotinib. Using whole-exome sequencing and RNAseq data, we identified four rare ALK fusion partners ( HIP1, GCC2, ERC1 , and SLC16A7 ) and one novel partner ( CEP55 ). At the mutation level, TP53 was the most frequently mutated gene and was only observed in patients with the shortest progression-free survival (PFS). Of note, only 4% of the genes carrying mutations are present in more than 1 patient. Analysis of somatic copy number aberrations (SCNA) demonstrated that a gain in EML4 was associated with longer PFS, and a loss of ALK or gain in EGFR was associated with shorter PFS. This study is the first to report a comprehensive view of the ALK+ NSCLC copy number landscape and to identify SCNA regions associated with clinical outcome. Our data show the presence of TP53 mutation as a strong prognostic indication of poor clinical response in ALK+ NSCLC. Furthermore, new and rare ALK fusion partners were observed in this cohort, expanding our knowledge in ALK+ NSCLC. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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