A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation Sequencing–Based Circulating Tumor DNA Profiling Exhibits Excellent Response.

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A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation Sequencing–Based Circulating Tumor DNA Profiling Exhibits Excellent Response to Crizotinib Yan Yang, MD, PhD, Shu-Kui Qin, MD, PhD, Jian Zhu, MD, Rui Wang, MD, Yu-Mei Li, MD, Zong-Yu Xie, MD, Qiong Wu, MD, PhD Mayo Clinic Proceedings: Innovations, Quality & Outcomes Volume 1, Issue 1, Pages 111-116 (July 2017) DOI: 10.1016/j.mayocpiqo.2017.04.003 Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 Imaging characteristics of the patient during chemotherapy. A, Chest CT scan after first-line chemotherapy showed enlarged paratracheal lymph nodes in the mediastinum and a nodule on the right pleura. B, Chest CT scan after 6 cycles of second-line chemotherapy showed tumor progression. CT = computed tomography. Mayo Clinic Proceedings: Innovations, Quality & Outcomes 2017 1, 111-116DOI: (10.1016/j.mayocpiqo.2017.04.003) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 Identification of STRN-ALK fusion in the patient’s paraffin-embedded surgical samples. A, Paired-end sequencing data from tumor tissue samples indicated somatic intrachromosomal STRN-ALK fusion as demonstrated by Integrative Genomics Viewer program. B, Confirmation of the STRN-ALK fusion by polymerase chain reaction. The expected product size is 166 bp. C, DNA sequence chromatograms show the conjoined regions at the DNA sequence level of the STRN-ALK fusion gene. D, Schematic diagram of the predicted domains of the STRN-ALK fusion protein. M = marker (100-bp ladder); NC = negative control; P = paraffin-embedded tissue sample. Mayo Clinic Proceedings: Innovations, Quality & Outcomes 2017 1, 111-116DOI: (10.1016/j.mayocpiqo.2017.04.003) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 3 Imaging characteristics of the patient during crizotinib treatment. Chest CT-enhanced scans were shown before (A) and 1 month (B), 2 months (C), and 6 months (D) after initiation of crizotinib therapy, demonstrating dramatic shrinkage of tumor lesions. E, Lumbar MRI after first-line therapy revealed an apparent enhancement of lesion at the L5 vertebral body after intensification, indicating the existence of bone metastases. F, Lumbar MRI after treatment with crizotinib for 2 months showed limited scope for reinforcement. MRI = magnetic resonance imaging. Mayo Clinic Proceedings: Innovations, Quality & Outcomes 2017 1, 111-116DOI: (10.1016/j.mayocpiqo.2017.04.003) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 4 Noninvasive detection and monitoring of ctDNA using targeted NGS. Dynamic changes in tumor burden (A) and carcinoembryonic antigen (B) in response to crizotinib treatment were closely correlated with alterations in fractional abundance of STRN-ALK in plasma. C, Concordance between different reporters (SNVs and fusion) in response to crizotinib. APC = adenomatous polyposis coli; CEA = carcinoembryonic antigen; ctDNA = circulating tumor DNA; MAF = mutant allele frequency; MAP2K1 = mitogen-activated protein kinase kinase 1; NGS = next-generation sequencing; SNV = single nucleotide variant; STAT3 = signal transducer and activator of transcription 3; TP53 = tumor protein 53. Mayo Clinic Proceedings: Innovations, Quality & Outcomes 2017 1, 111-116DOI: (10.1016/j.mayocpiqo.2017.04.003) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions