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Case Reports
. 2021 Aug 19:11:700341.
doi: 10.3389/fonc.2021.700341. eCollection 2021.

STK3-ALK, a Novel ALK Rearrangement in Non-Small Cell Lung Cancer With Sensitivity to Tyrosine Kinase Inhibitors: A Case Report

Chunlai Feng  1 , Rong Zhou  1 , Feng Liu  1 , Tingting Wang  2 , Sisi Liu  2 , Yang Shao  2
Affiliations
Case Reports

STK3-ALK, a Novel ALK Rearrangement in Non-Small Cell Lung Cancer With Sensitivity to Tyrosine Kinase Inhibitors: A Case Report

Chunlai Feng et al. Front Oncol. .

Abstract

Anaplastic lymphoma kinase (ALK) rearrangement occurs in 5% to 8% of patients with non-small cell lung cancer (NSCLC). More than 90 different ALK fusion partners have been discovered in NSCLC patients, and ALK tyrosine kinase inhibitors (TKIs) such as crizotinib and alectinib have achieved tumor responses in patients with advanced ALK-positive NSCLC. Here, we report the case of a patient with an advanced NSCLC carrying a novel serine/threonine kinase 3 (STK3)-ALK rearrangement, which was identified by targeted next-generation sequencing (NGS) and was confirmed by RNA sequencing. Anti-ALK immunohistochemistry (IHC) staining also revealed the high expression of ALK. The patient benefitted from alectinib treatment after experiencing crizotinib resistance and achieved an overall response to TKI of over 14 months. At the timepoint of submission of this manuscript, this patient is still receiving alectinib treatment with a good tolerance. This study provides meaningful insights into the potential treatment option for NSCLC patients with brain metastases harboring STK3-ALK fusions and highlights the advantages of NGS in rapidly identifying novel molecular targets.

Keywords: ALK rearrangement; NSCLC; STK3-ALK; TKI; brain metastases; case report.

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Conflict of interest statement

TW, SL, and YS are employees of Nanjing Geneseeq Technology Inc., China. 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.

Figures

Figure 1
Figure 1
Representative clinical images obtained during the course of treatment. (A) FDG-PET/CT of the brain, lung, and mediastinum before (2020/02) and after (2021/04) TKI therapy. (B) Hematoxylin and eosin (HE) staining of the tumor biopsy revealed a few atypical glands. Immunohistochemical staining of thyroid transcription factor (TTF1) (C), p40 (D), and Ki-67 (E) of the tumor biopsy (400×).
Figure 2
Figure 2
Sequence analysis of the STK3-ALK fusion. (A) DNA and (B) RNA-level fusion reads of STK3-ALK are shown from the Integrative Genomics Viewer. (C) A schematic map showing the structure of the STK3-ALK fusion locus. Exons 1–6 of STK3 (purple) were fused to exons 20–29 of ALK (green) through intron6 of STK3 and intron19 of ALK. (D) Immunohistochemical staining revealed the diffuse expression of ALK in tumor cells (20×).
Figure 3
Figure 3
Radiological features before and after crizotinib therapy. (A) Timeline of therapies for advanced NSCLC. (B) The chest CT and brain MRI scans reveal the control of disease after crizotinib treatment. Tumors are indicated by red arrows. CT, computed tomography; MRI, magnetic resonance imaging; SRS, stereotactic radiosurgery; MAF, mutant allele frequency; SD, stable disease; PD, progressive disease.
See this image and copyright information in PMC

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