scholarly journals Are Anaplastic Lymphoma Kinase Gene Rearrangements in Non-small Cell Lung Cancer Prognostic, Predictive, or Both?

2012 ◽  
Vol 7 (1) ◽  
pp. 5-7 ◽  
Author(s):  
Benjamin Solomon ◽  
Alice T. Shaw
2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11595-11595
Author(s):  
Jeffrey S. Ross ◽  
Siraj Mahamed Ali ◽  
Julia Andrea Elvin ◽  
Alexa Betzig Schrock ◽  
James Suh ◽  
...  

11595 Background: Genomic fusions of the anaplastic lymphoma kinase gene ( ALK) are an established therapy target for patients with non-small cell lung cancer (NSCLC), but are not well-characterized in non-NSCLC malignancies. Methods: Comprehensive genomic profiling (CGP) of 92,784 clinically advanced malignancies was performed using a hybrid-capture, adaptor ligation based NGS assay to a mean coverage depth of >600X. Tumor mutational burden (TMB) was calculated from a minimum of 1.1 Mb of sequenced DNA. Results: 17,127/92,784 (18.5%) were NSCLC and 75,657 (81.5%) were non-NSCLC. Of the 697 (0.8%) of cases with ALK fusions, 554 (79%) were identified in NSCLC and 143 (21%) in non-NSCLC including 67 carcinomas; 39 sarcomas including 30 non-uterine and uterine leiomyosarcomas and inflammatory myofibroblastic tumors; 24 in hematolymphoid malignancies including non-Hodgkins lymphomas, myelomas and histiocytic malignancies; 3 in gliomas; 2 each in mesotheliomas, neuroblastomas and undifferentiated malignancies and 1 in melanoma. ALK fusions were significantly more frequently identified in NSCLC (3.2%) than in non-NSCLC (p<0.0001). The non-NSCLC ALK fusion positive patients were significantly older (p<0.0001) and more often female (p<0.0001) than the NSCLC ALK fusion positive patients. At 84%, the more frequent finding of EML4 as the fusion partner in the NSCLC patients versus non-NSCLC patients at 31% was significant (p<0.0001). ALK fusion positive non-NSCLC had significantly lower TMB (mean 5.01 mutations/Mb) than non- ALK altered non-NSCLC (p=0.006). Non-NSCLC ALKfusion positive cases responding to ALK inhibitors will be presented. Conclusions: In non-NSCLC patients ALK fusions are rare and found in both epithelial and mesenchymal malignancies. Initial evidence strongly suggests that anti-ALK therapies can be effective in ALK fusion driven non-NSCLC .


2020 ◽  
Vol 50 (6) ◽  
pp. 716-725
Author(s):  
Mark J. McKeage ◽  
Sandar Tin Tin ◽  
Prashannata Khwaounjoo ◽  
Karen Sheath ◽  
Amanda Dixon‐McIver ◽  
...  

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