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2 "Lu Shen"
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Breast cancer
Genomic Characteristics and Its Therapeutic Implications in Breast Cancer Patients with Detectable Molecular Residual Disease
Shu Zhang, Yan Jiang, Lu Zhou, Jing Xu, Gang Zhang, Lu Shen, Yan Xu
Cancer Res Treat. 2024;56(2):538-548.   Published online December 5, 2023
DOI: https://doi.org/10.4143/crt.2023.1059
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Molecular residual disease (MRD) is the main cause of postoperative recurrence of breast cancer. However, the baseline tumor genomic characteristics and therapeutic implications of breast cancer patients with detectable MRD after surgery are still unknown.
Materials and Methods
In this study, we enrolled 80 patients with breast cancer who underwent next-generation sequencing-based genetic testing of 1,021 cancer-related genes performed on baseline tumor and postoperative plasma, among which 18 patients had detectable MRD after surgery.
Results
Baseline clinical characteristics found that patients with higher clinical stages were more likely to have detectable MRD. Analysis of single nucleotide variations and small insertions/deletions in baseline tumors showed that somatic mutations in MAP3K1, ATM, FLT1, GNAS, POLD1, SPEN, and WWP2 were significantly enriched in patients with detectable MRD. Oncogenic signaling pathway analysis revealed that alteration of the Cell cycle pathway was more likely to occur in patients with detectable MRD (p=0.012). Mutational signature analysis showed that defective DNA mismatch repair and activation-induced cytidine deaminase (AID) mediated somatic hypermutation (SHM) were associated with detectable MRD. According to the OncoKB database, 77.8% (14/18) of patients with detectable MRD had U.S. Food and Drug Administration–approved mutational biomarkers and targeted therapy.
Conclusion
Our study reports genomic characteristics of breast cancer patients with detectable MRD. The cell cycle pathway, defective DNA mismatch repair, and AID-mediated SHM were found to be the possible causes of detectable MRD. We also found the vast majority of patients with detectable MRD have the opportunity to access targeted therapy.
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Lung and Thoracic cancer
Genomic Characteristics and the Potential Clinical Implications in Oligometastatic Non–Small Cell Lung Cancer
Rongxin Liao, Kehong Chen, Jinjin Li, Hengqiu He, Guangming Yi, Mingfeng Huang, Rongrong Chen, Lu Shen, Xiaoyue Zhang, Zaicheng Xu, Zhenzhou Yang, Yuan Peng
Cancer Res Treat. 2023;55(3):814-831.   Published online January 12, 2023
DOI: https://doi.org/10.4143/crt.2022.1315
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis.
Materials and Methods
We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity.
Results
We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation.
Conclusion
Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

Citations

Citations to this article as recorded by  
  • Prognostic and Predictive Biomarkers of Oligometastatic NSCLC: New Insights and Clinical Applications
    Mandy Jongbloed, Martina Bortolot, Leonard Wee, Jarno W.J. Huijs, Murillo Bellezo, Rianne D.W. Vaes, Frank Aboubakar Nana, Koen J. Hartemink, Dirk K.M. De Ruysscher, Lizza E.L. Hendriks
    JTO Clinical and Research Reports.2024; 5(12): 100740.     CrossRef
  • Genomic characteristics of PD-L1-Induced resistance to EGFR-TKIs in lung adenocarcinoma
    Guangming Yi, Fanghao Cai, Liangzhong Liu, Rongxin Liao, Xuan Jiang, Zhenzhou Yang, Xiaoyue Zhang
    Future Oncology.2024; 20(40): 3477.     CrossRef
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