Details

Autor(en) / Beteiligte

• Nguyen, Hoai-Nghia
• Cao, Ngoc-Phuong Thi
• Van Nguyen, Thien-Chi
• Le, Khang Nguyen Duy
• Nguyen, Dat Thanh
• Nguyen, Quynh-Tho Thi
• Nguyen, Thai-Hoa Thi
• Van Nguyen, Chu
• Le, Ha Thu
• Nguyen, Mai-Lan Thi
• Nguyen, Trieu Vu
• Tran, Vu Uyen
• Luong, Bac An
• Le, Linh Gia Hoang
• Ho, Quoc Chuong
• Pham, Hong-Anh Thi
• Vo, Binh Thanh
• Nguyen, Luan Thanh
• Dang, Anh-Thu Huynh
• Nguyen, Sinh Duy
• Do, Duc Minh
• Do, Thanh-Thuy Thi
• Hoang, Anh Vu
• Dinh, Kiet Truong
• Phan, Minh-Duy
• Giang, Hoa
• Tran, Le Son

Titel

Liquid biopsy uncovers distinct patterns of DNA methylation and copy number changes in NSCLC patients with different EGFR-TKI resistant mutations

Ist Teil von

• Scientific reports, 2021-08, Vol.11 (1), p.16436-16436, Article 16436

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops after treatment. Although genetic and epigenetic alterations have each been shown to drive resistance to TKI in cell line models, clinical evidence for their contribution in the acquisition of resistance remains limited. Here, we employed liquid biopsy for simultaneous analysis of genetic and epigenetic changes in 122 Vietnamese NSCLC patients undergoing TKI therapy and displaying acquired resistance. We detected multiple profiles of resistance mutations in 51 patients (41.8%). Of those, genetic alterations in EGFR, particularly EGFR amplification (n = 6), showed pronounced genome instability and genome-wide hypomethylation. Interestingly, the level of hypomethylation was associated with the duration of response to TKI treatment. We also detected hypermethylation in regulatory regions of Homeobox genes which are known to be involved in tumor differentiation. In contrast, such changes were not observed in cases with MET (n = 4) and HER2 (n = 4) amplification. Thus, our study showed that liquid biopsy could provide important insights into the heterogeneity of TKI resistance mechanisms in NSCLC patients, providing essential information for prediction of resistance and selection of subsequent treatment.