Reference Detail

Ref Type

Journal Article

PMID

(30154667)

Authors

Zheng Q, Zheng M, Jin Y, Shen X, Shan L, Shen L, Sun Y, Chen H, Li Y

Title

ALK-rearrangement neuroendocrine carcinoma of the lung: a comprehensive study of a rare case series and review of literature.

Journal	Vol	Issue	Date	Pages	Journal Short Title
OncoTargets and therapy	11		2018	4991-4998	Onco Targets Ther

URL

Abstract Text

Driver mutations involving tyrosine kinase receptors play crucial roles in the oncogenesis of lung adenocarcinoma. However, receptor tyrosine kinase mutations are extremely rare events in primary pulmonary neuroendocrine carcinoma (NEC), which is a molecular heterogeneous entity. In this study, we examined 4 cases of NEC with anaplastic lymphoma kinase (ALK) rearrangement between 2008 and 2018 at our hospital. We comprehensively analyzed the carcinomas' clinicopathological features, genetic alterations, and response to ALK inhibitor. One case of atypical carcinoid tumor and 1 case of large cell NEC (LCNEC) achieved response to ALK inhibitor (crizotinib) treatment. One case of combined LCNEC with adenocarcinoma harboring KLC1-ALK (K9:A20) fusion genes was confirmed by NGS of both components, while only the LCNEC component presented RB1 mutation. Notably, tumor cells of different components exhibited different ALK-positive signal patterns by fluorescence in situ hybridization, which revealed isolated 3' signals in the adenocarcinoma component but split signals in the LCNEC. As the largest case series study, our findings suggested that preliminary screening for ALK rearrangement should also be considered in atypical carcinoid and high-grade NEC. Patients with ALK rearrangement-positive NEC would benefit from ALK inhibitor intervention.

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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

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
EML4 - ALK	neuroendocrine tumor	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, first-line treatment with Xalkori (crizotinib) resulted in shrinkage of the lung and adrenal gland lesions in a patient with a neuroendocrine tumor, consistent with atypical carcinoid tumor, harboring EML4-ALK (PMID: 30154667).	30154667
EML4 - ALK	large cell neuroendocrine carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a clinical case study, Xalkori (crizotinib) treatment resulted in regression of all previously identified lesions in a patient with large cell neuroendocrine carcinoma harboring EML4-ALK (PMID: 30154667).	30154667