Identification of a novel ALK variant intrinsically resistant to crizotinib
The knowledge of oncogene addiction in non small cell lung carcinoma (NSCLC) involving EGFR, ALK and ROS1 genes has changed the therapeutic and prognostic landscape of NSCLC. ALK rearranged NSCLC accounts for 10% of these cases, and with the development and approval of ALK TKIs (tyrosine kinase inhi...
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2020-12-01
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doaj-f7ae95c7b8e24b26b3563cb43cb0d3572021-09-03T04:48:09ZengElsevierCurrent Problems in Cancer: Case Reports2666-62192020-12-012100040Identification of a novel ALK variant intrinsically resistant to crizotinibUllas Batra0Shrinidhi Nathany1Mansi Sharma2Satyajeet Soni3Parveen Jain4Sunil Pasricha5Abhishek Bansal6Anurag Mehta7Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Center, Sector 5, Rohini, New Delhi 110085, India; Corresponding author.Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, IndiaDepartment of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Center, Sector 5, Rohini, New Delhi 110085, IndiaDepartment of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Center, Sector 5, Rohini, New Delhi 110085, IndiaDepartment of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Center, Sector 5, Rohini, New Delhi 110085, IndiaDepartment of Pathology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, IndiaDepartment of Radiology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, IndiaLaboratory Services, Molecular Diagnostics and Transfusion Medicine, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, IndiaThe knowledge of oncogene addiction in non small cell lung carcinoma (NSCLC) involving EGFR, ALK and ROS1 genes has changed the therapeutic and prognostic landscape of NSCLC. ALK rearranged NSCLC accounts for 10% of these cases, and with the development and approval of ALK TKIs (tyrosine kinase inhibitors) like crizotinib, it is imperative to detect the same. Various ALK variants are known to occur resulting in differential sensitivities to TKIs because of different protein stabilities. The precise characterization hence is important which can be achieved only by high throughput next generation sequencing (NGS) based assays. Immunohistochemistry and FISH (fluorescence in situ hybridization) although considered gold standards cannot define the breakpoints and length of the fusion transcripts. We herein report a novel EML4-ALK variant in a case of advanced NSCLC which plausibly is inherently resistant to crizotinib because of the breakpoints involved.http://www.sciencedirect.com/science/article/pii/S2666621920300405ALK rearranged NSCLCCrizotinib resistanceNovel variant |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ullas Batra Shrinidhi Nathany Mansi Sharma Satyajeet Soni Parveen Jain Sunil Pasricha Abhishek Bansal Anurag Mehta |
spellingShingle |
Ullas Batra Shrinidhi Nathany Mansi Sharma Satyajeet Soni Parveen Jain Sunil Pasricha Abhishek Bansal Anurag Mehta Identification of a novel ALK variant intrinsically resistant to crizotinib Current Problems in Cancer: Case Reports ALK rearranged NSCLC Crizotinib resistance Novel variant |
author_facet |
Ullas Batra Shrinidhi Nathany Mansi Sharma Satyajeet Soni Parveen Jain Sunil Pasricha Abhishek Bansal Anurag Mehta |
author_sort |
Ullas Batra |
title |
Identification of a novel ALK variant intrinsically resistant to crizotinib |
title_short |
Identification of a novel ALK variant intrinsically resistant to crizotinib |
title_full |
Identification of a novel ALK variant intrinsically resistant to crizotinib |
title_fullStr |
Identification of a novel ALK variant intrinsically resistant to crizotinib |
title_full_unstemmed |
Identification of a novel ALK variant intrinsically resistant to crizotinib |
title_sort |
identification of a novel alk variant intrinsically resistant to crizotinib |
publisher |
Elsevier |
series |
Current Problems in Cancer: Case Reports |
issn |
2666-6219 |
publishDate |
2020-12-01 |
description |
The knowledge of oncogene addiction in non small cell lung carcinoma (NSCLC) involving EGFR, ALK and ROS1 genes has changed the therapeutic and prognostic landscape of NSCLC. ALK rearranged NSCLC accounts for 10% of these cases, and with the development and approval of ALK TKIs (tyrosine kinase inhibitors) like crizotinib, it is imperative to detect the same. Various ALK variants are known to occur resulting in differential sensitivities to TKIs because of different protein stabilities. The precise characterization hence is important which can be achieved only by high throughput next generation sequencing (NGS) based assays. Immunohistochemistry and FISH (fluorescence in situ hybridization) although considered gold standards cannot define the breakpoints and length of the fusion transcripts. We herein report a novel EML4-ALK variant in a case of advanced NSCLC which plausibly is inherently resistant to crizotinib because of the breakpoints involved. |
topic |
ALK rearranged NSCLC Crizotinib resistance Novel variant |
url |
http://www.sciencedirect.com/science/article/pii/S2666621920300405 |
work_keys_str_mv |
AT ullasbatra identificationofanovelalkvariantintrinsicallyresistanttocrizotinib AT shrinidhinathany identificationofanovelalkvariantintrinsicallyresistanttocrizotinib AT mansisharma identificationofanovelalkvariantintrinsicallyresistanttocrizotinib AT satyajeetsoni identificationofanovelalkvariantintrinsicallyresistanttocrizotinib AT parveenjain identificationofanovelalkvariantintrinsicallyresistanttocrizotinib AT sunilpasricha identificationofanovelalkvariantintrinsicallyresistanttocrizotinib AT abhishekbansal identificationofanovelalkvariantintrinsicallyresistanttocrizotinib AT anuragmehta identificationofanovelalkvariantintrinsicallyresistanttocrizotinib |
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1717817904296099840 |