Dataset Information

Novel ETV1 mutation in small cell lung cancer transformation resistant to EGFR tyrosine kinase inhibitors.

ABSTRACT:

Background

Non-small cell lung cancer (NSCLC) patients harboring mutations in the epidermal growth factor receptor (EGFR) gene respond dramatically to EGFR tyrosine kinase inhibitors (TKIs). However, these patients inevitably develop acquired resistance to EGFR-TKIs. Among them, small cell lung cancer (SCLC) transformation is a relatively rare mechanism.

Methods

We used a 639 cancer-relevant gene panel to detect genetic differences in tissues before and after EGFR-TKIs resistance caused by SCLC transformation. In vitro experiments were conducted to study the role of ETS variant transcription factor 1 (ETV1) on SCLC transformation and EGFR-TKIs resistance.

Results

We present two EGFR-mutant lung adenocarcinoma (LUAD) patients. One patient, with EGFR exon 19 deletion (Ex19del), accepted first-line gefitinib treatment and then received osimertinib treatment due to acquisition of an EGFR-T790M mutation. A novel ETV1 mutation (p.P159S) was detected in the SCLC tissue after osimertinib resistance when not coexisting with T790M. The other patient harbored an EGFR exon 21 mutation (p.L858R), and had a long-lasting response to first-line gefitinib, and then transformed to SCLC after TKI resistance. A previously unreported ETV1 mutation (p.E462Q) was detected in the SCLC tissue. In vitro, ETV1 p.E462Q and p.P159S mutations participated in neuroendocrine differentiation by inducing the expression of achaete-scute homolog 1 (ASCL1) and promoting the proliferation of H69 cells. ETV1 p.E462Q and p.P159S mutations were also resistant to gefitinib and osimertinib after introduction into H358 cells.

Conclusions

Novel ETV1 p.E462Q and p.P159S mutations were found in the SCLC tissues of TKIs-resistant LUAD patients, providing a new understanding of ETV1 involvement in acquired resistance to EGFR-TKIs via SCLC transformation.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC8350694 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Novel ETV1 mutation in small cell lung cancer transformation resistant to EGFR tyrosine kinase inhibitors.

Zhou Yan Y Bai Hao H Xia Jinjing J Xu Wang-Yang WY Cheng Lei L Xiong Liwen L

Annals of translational medicine 20210701 14

<h4>Background</h4>Non-small cell lung cancer (NSCLC) patients harboring mutations in the epidermal growth factor receptor (<i>EGFR</i>) gene respond dramatically to <i>EGFR</i> tyrosine kinase inhibitors (TKIs). However, these patients inevitably develop acquired resistance to <i>EGFR</i>-TKIs. Among them, small cell lung cancer (SCLC) transformation is a relatively rare mechanism.<h4>Methods</h4>We used a 639 cancer-relevant gene panel to detect genetic differences in tissues before and after ...[more]

PMID: 34430591

Similar Datasets

Project description:BackgroundLung adenocarcinoma can transform into small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. Approximately 3% to 10% of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) could transform to SCLC. This phenomenon has been described in several case reports and small patient series. However, the characteristics and treatment outcomes of this population have not been comprehensively reported, and their clinical course is poorly characterized.MethodsWe performed a systematic review of the published literature to summarize the clinical and pathological features and prognosis of the reported cases and analyzed the demographics, disease features, and outcomes.ResultsA total of 72 patients (50 females and 22 males) initially diagnosed with lung adenocarcinoma were included. EGFR mutations included 19-deletion (75%), L858R (22%), and G719X (3%). All patients received EGFR-TKIs before SCLC transformation. The median time from diagnosis to transformation was 20.5 months (95% CI, 15.45 to 26.55 months). Of the 67 patients with post-translational gene test results, 58 maintained their EGFR mutation, and only 1 of 18 with prior T790M positivity retained T790M mutation. After the pathological transformation, both conventional chemotherapy regimen and chemotherapy combined targeted therapy yielded high response rates. The disease control rate of first-line therapy after transformation was 76%, while the objective response rate was 48%. The median overall survival (OS) since diagnosis was 27 months (95% CI, 22.90 to 31.10 months), whereas median OS since SCLC transformation was 8.5 months (95% CI, 5.50 to 11.60 months).ConclusionThe prognosis of transformed SCLC is worse than primary SCLC. The response rate to conventional chemotherapy was high. However, the progression-free survival and OS after transformation were short and the prognosis was poor with first-line therapies. New therapies are needed in the management of transformed SCLC.

Dataset Information

Novel ETV1 mutation in small cell lung cancer transformation resistant to EGFR tyrosine kinase inhibitors.

Background

Methods

Results

Conclusions

Publications

Novel ETV1 mutation in small cell lung cancer transformation resistant to EGFR tyrosine kinase inhibitors.

Similar Datasets

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