Lung adenocarcinoma harboring concomitant SPTBN1-ALK fusion, c-Met overexpression, and HER-2 amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy

Abstract

Crizotinib is a multi-targeted tyrosine kinase inhibitor (TKI) with activity against mesenchymal-epithelial transition factor (MET) and anaplastic lymphoma kinase (ALK). However, the concomitant oncogenic drivers may affect the sensitivity of crizotinib. Herein, we present a 69-year-old never-smoker Chinese male with advanced lung adenocarcinoma harboring concomitant spectrin beta non-erythrocytic 1 (SPTBN1)-ALK fusion, c-Met overexpression, and human epidermal growth factor receptor-2 (HER-2) amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy. Although the patient received timely and comprehensive treatment, the overall survival was only 8 months. Therefore, c-Met overexpression, HER-2 gene amplification, and SPTBN1-ALK gene fusion can coexist in lung adenocarcinoma and may become a potential biomarker of cancer refractory to crizotinib, chemotherapy, and radiotherapy as well as of a relatively poor prognosis. In addition, the novel SPTBN1-ALK fusion gene may become a potential target for anti-tumor therapy.

Keywords: Chemotherapy; Crizotinib; HER-2; Lung adenocarcinoma; NSCLC; Oncogenic drivers; Radiotherapy; SPTBN1-ALK; c-Met.

Fig. 1

Lung biopsy specimens and total-body PET/CT scan before treatment. Hematoxylin and eosin (H & E) staining (magnification ×200, a), IHC of c-Met (magnification ×200, b), and ALK (magnification ×100, c) of a diagnostic biopsy specimen. Total-body PET/CT showed a 5.1 × 3.7 cm-sized tumor in the right upper lobe (d) with the second lumbar and left ilium metastases (arrowheads, e, f)

Fig. 2

Hypothetical structure of SPTBN1-ALK fusion gene. SPTBN1-ALK fusion gene was formed by placing SPTBN1 exons 1–6 upstream of ALK exons 20–29, which were separated by small genomic shards