Partial Response to Crizotinib in a Lung Adenocarcinoma Patient with a Novel FBXO11 (Intergenic)-ALK (Exon 20-29) Fusion

Abstract

Intergenic-gene fusion detected by DNA-seq is particularly confusing for drug selection since the function of the intergenic region located upstream is unknown. We reported a case of a 49-year-old male with advanced lung adenocarcinoma, who was detected FBXO11 (intergenic)-ALK (exon 20-29) by DNA-seq, and FISH analysis revealed a positive result. The patient was treated with crizotinib and achieved a PR. The canonical EML4 (exon 1-13)-ALK (exon 20-29) fusion verified by RNA-seq suggested a complex EML4 (exon 1-13)-FBXO11 (intergenic)-ALK (exon 20-29) tripartite rearrangement at the DNA level. Our case emphasized the necessity of RNA-seq for verifying intergenic-gene fusion. Simultaneously, the pathogenic germline SLX4 variant and extensive CNVs of DNA segment were detected by DNA-seq deserves our attention.

Keywords:

• intergenic fusion
• lung adenocarcinoma
• ALK
• SLX4
• chromothripsis

Abbreviations

NSCLC, non-small-cell lung cancer; TKIs, tyrosine kinase inhibitors; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; DNA-seq, DNA sequencing; RNA-seq, RNA sequencing; NGS, next-generation sequencing; CT, computed tomography; UICC, Union of International Cancer Control; PFS, progression-free survival; OS, overall survival; HR, homologous recombination; CNVs, copy number variations.

Data Sharing Statement

The original contributions presented in the study are included in the article, and further inquiries can be directed to the corresponding author.

Ethics Approval and Informed Consent

The authors declare that written informed consent was obtained from the patient’s and institutional approval for the publication of data and images. The research gene analysis was with ethics approval (HREC ID 4814).

Consent for Publication

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

We thank Dr. Ran Ding, Siqi Chen, Dr. Chuang Qi, Dr. Dongsheng Chen and Dr. Wanglong Deng from Jiangsu Simcere Diagnostics for their kind assistance. Jing He and Youyuan Yao are co-first authors for this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Fei Quan and Zhongyu Lu were employed by Jiangsu Simcere Diagnostics Co., Ltd during the conduct of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.