Intergenic breakpoints identified by DNA sequencing confound targetable kinase fusion detection in non-small cell lung cancer

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Weihua LiJianming Ying

Abstract

Next-generation sequencing (NGS) based on genomic DNA has been widely applied for gene rearrangement detection in patients with non-small cell lung cancer (NSCLC). However, intergenic-breakpoint fusions, in which one or both genomic breakpoints localize to intergenic regions, confound kinase fusion detection. We evaluated the function of intergenic-breakpoint fusions with multiplex molecular testing approaches. NSCLCs with intergenic-breakpoint fusion identified by DNA-based NGS were analyzed by RNA-based NGS, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Twenty-six cases with single intergenic-breakpoint fusion were identified from a large cohort of NSCLCs using DNA-based NGS. Of the 26 cases, RNA-based NGS detected expressed fusion transcripts in 11 cases, and the genomic breakpoint position did not logically predict breakpoint of the fusion transcript in these cases, possibly due to complex rearrangements (n=5), alternative splicing (n=2) and reciprocal rearrangement (n=4). Nonetheless, no expressed fusion transcript was detected in 5 cases. Moreover, positive ALK IHC was observed in 3 of the remaining 10 cases without RNA-based NGS results. Three intergenic-breakpoint ALK fusion cases with or wit...Continue Reading

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Citations

Dec 15, 2020·Critical Reviews in Oncology/hematology·Evgeny N ImyanitovEvgeny V Levchenko
Feb 6, 2021·Journal of Cancer Research and Clinical Oncology·Yawei DouHongtao Wang
Jan 10, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Guojiang ZhaoShengli Yang
Jan 15, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Chengzhi CaiMeijuan Huang
Nov 29, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Weihua LiJianming Ying
Mar 2, 2021·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Zhengbo SongZongli Zheng
Mar 22, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Donghua ZhaoYongjie Wang
Mar 16, 2021·Expert Review of Anticancer Therapy·Federica Zito MarinoRenato Franco
Jul 1, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Susan J Hsiao, Sai-Hong Ignatius Ou
Jul 17, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jiexia ZhangRongrong Chen

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