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Ref Type Journal Article
PMID (35144623)
Authors Tao H, Liu Z, Mu J, Gai F, Huang Z, Shi L
Title Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively.
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Abstract Text Anaplastic lymphoma kinase (ALK) gene rearrangements, have been identified in approximately 2-7% of patients with lung adenocarcinoma (LUAD). However, co-occurrence of double ALK fusions in one patient was rare. Herein, we reported two Chinese female LUAD patients with confirmed double ALK fusion variants by next generation sequencing.Case 1, a 38-year-old female was diagnosed as peripheral LUAD in left upper lobe with synchronous multiple intrapulmonary metastases (pT2N0M1b, stage IVa). And case 2, a 58-year-old female had left lower lobe primary LUAD and synchronous multiple lung metastases (pT4N2M1b, stage IVa). In both patients, tumor cells displayed strong expression of ALK protein. Genetic profiling by next generation sequencing showed both patients concurrently harbored two types of ALK rearrangements. Case 1 had an unreported ALK-SSH2/EML4-ALK double fusions, and case 2 had an another novel ARID2-ALK/EML4-ALK double fusions. Both of these patients responded to ALK inhibitor crizotinib.Our study reported two novel ALK fusion partners never reported, which expands the knowledge of ALK fusion spectrum and provides insight into therapeutic options for patients with double ALK fusions.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
ARID2 ALK ARID2 - ALK fusion unknown ARID2-ALK results from the fusion of ARID2 and ALK (PMID: 35144623). ARID2-ALK has been identified in lung adenocarcinoma (PMID: 35144623), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, May 2024).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ARID2 - ALK EML4 - ALK lung adenocarcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in stable disease for 12 months in a lung adenocarcinoma patient harboring two ALK fusions, EML4-ALK (e20:e20) and ARID2-ALK (e12:e23) (PMID: 35144623). 35144623