Reference Detail

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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Diagnostic pathology	17	1	2022 Feb 10	27	Diagn Pathol

URL

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