Research Papers:

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

William C.S. Cho _, Kien Thiam Tan, Victor W.S. Ma, Jacky Y.C. Li, Roger K.C. Ngan, Wah Cheuk, Timothy T.C. Yip, Yi-Ting Yang and Shu-Jen Chen

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Oncotarget. 2018; 9:36344-36357. https://doi.org/10.18632/oncotarget.26349

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William C.S. Cho1, Kien Thiam Tan2, Victor W.S. Ma1, Jacky Y.C. Li1, Roger K.C. Ngan3, Wah Cheuk4, Timothy T.C. Yip5, Yi-Ting Yang2 and Shu-Jen Chen2

1Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong

2ACT Genomics, Co. Ltd., Taipei, Taiwan

3Department of Clinical Oncology, The University of Hong Kong, Gleneagles Hong Kong Hospital, Wong Chuk Hang, Hong Kong

4Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong

5ACT Genomics, Co. Ltd., Kowloon, Hong Kong

Correspondence to:

William C.S. Cho, email: [email protected] or [email protected]

Yi-Ting Yang, email: [email protected]

Shu-Jen Chen, email: [email protected]

Keywords: biomarker; early-stage; lung cancer; next-generation sequencing; relapse

Received: August 20, 2018     Accepted: November 01, 2018     Published: November 20, 2018


Purpose: The identification of genomic alterations related to recurrence in early-stage non-small cell lung cancer (NSCLC) patients may help better stratify high-risk individuals and guide treatment strategies. This study aimed to identify the molecular biomarkers of recurrence in early-stage NSCLC.

Results: Of the 42 tumors evaluable for genomic alterations, TP53 and EGFR were the most frequent alterations with population frequency 52.4% and 50.0%, respectively. Fusion genes were detected in four patients, which had lower mutational burden and relatively better genomic stability. EGFR mutation and fusion gene were mutually exclusive in this study. CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were only observed in the relapsed patients. Increased copy number alteration index was observed in early relapsed patients. Among these genomic alterations, early-stage NSCLCs harboring CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were found to be significantly associated with recurrence. Some of these new findings were validated using The Cancer Genome Atlas (TCGA) dataset.

Conclusions: The genomic alterations of CDKN2A, FAS, SUFU and SMARCA4 in early-stage NSCLC are found to be associated with recurrence, but confirmation in a larger independent cohort is required to define the clinical impact.

Materials and Methods: Paired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A panel targets exons for 440 genes was used to assess the mutational and copy number status of selected genes in three clinically relevant groups of stage I/II NSCLC patients: 1) Early relapse; 2) Late relapse; and 3) No relapse.

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