المؤلفون: Yang, Po-Sheng, Chao, Ying-Ting, Lung, Chun-Fan, Liu, Chien-Liang, Chang, Yuan-Ching, Li, Ker-Chau, Hsu, Yi-Chiung

المساهمون: Academia Sinica, Ministry of Science and Technology, Taiwan, Mackay Memorial Hospital, National Health Research Institutes

المصدر: Frontiers in Oncology ; volume 12 ; ISSN 2234-943X

الوصف: Breast cancer is the most common invasive cancer in women worldwide. Next-generation sequencing (NGS) provides a high-resolution profile of cancer genome. Our study ultimately gives the insight for genetic screening to identify the minority of patients with breast cancer with a poor prognosis, who might benefit from the most intensive possible treatment. The detection of mutations can polish the traditional method to detect high-risk patients who experience poor prognosis, recurrence and death early. In total, 147 breast cancer tumors were sequenced with targeted sequencing using a RainDance Cancer Hotspot Panel. The average age of all 147 breast cancer patients in the study was 51.7 years, with a range of 21–77 years. The average sequencing depth was 5,222x (range 2,900x-8,633x), and the coverage was approximately 100%. A total of 235 variants in 43 genes were detected in 147 patients by high-depth Illumina sequencing. A total of 219 single nucleotide variations were found in 42 genes from 147 patients, and 16 indel mutations were found in 13 genes from 84 patients. After filtering with the 1000 Genomes database and for synonymous SNPs, we focused on 54 somatic functional point mutations. The functional point mutations contained 54 missense mutations in 22 genes. Additionally, mutation of genes within the RET, PTEN, CDH1, MAP2K4, NF1, ERBB2, RUNX1, PIK3CA, FGFR3, KIT, KDR, APC, SMO, NOTCH1, and FBXW7 in breast cancer patients were with poor prognosis. Moreover, TP53 and APC mutations were enriched in triple-negative breast cancer. APC mutations were associated with a poor prognosis in human breast cancer (log-rank P<0.001). Our study identified tumor mutation hotspot profiles in Taiwanese breast cancer patients, revealing new targetable gene mutations in Asian breast cancer patients.

الإتاحة: https://doi.org/10.3389/fonc.2022.819555Test

المؤلفون: Jiang, Runze, Lu, Yi-Tsung, Ho, Hao, Li, Bo, Chen, Jie-Fu, Lin, Millicent, Li, Fuqiang, Wu, Kui, Wu, Hanjie, Lichterman, Jake, Wan, Haolei, Lu, Chia-Lun, OuYang, William, Ni, Ming, Wang, Linlin, Li, Guibo, Lee, Tom, Zhang, Xiuqing, Yang, Jonathan, Rettig, Matthew, Chung, Leland WK, Yang, Huanming, Li, Ker-Chau, Hou, Yong, Tseng, Hsian-Rong, Hou, Shuang, Xu, Xun, Wang, Jun, Posadas, Edwin M

المصدر: Oncotarget. 6(42)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Biotechnology, Urologic Diseases, Clinical Research, Human Genome, Prostate Cancer, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Base Sequence, Biomarkers, Tumor, Biopsy, Cell Separation, Chromosomes, Human, DNA Mutational Analysis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Laser Capture Microdissection, Liver Neoplasms, Male, Molecular Sequence Data, Mutation, Nanotechnology, Neoplastic Cells, Circulating, Oligonucleotide Array Sequence Analysis, Phenotype, Polymorphism, Single Nucleotide, Predictive Value of Tests, Prostatic Neoplasms, Time Factors, circulating tumor cell, prostate cancer, whole genome sequencing, liquid biopsy, cancer heterogeneity, Oncology and carcinogenesis

الوصف: Previous studies have demonstrated focal but limited molecular similarities between circulating tumor cells (CTCs) and biopsies using isolated genetic assays. We hypothesized that molecular similarity between CTCs and tissue exists at the single cell level when characterized by whole genome sequencing (WGS). By combining the NanoVelcro CTC Chip with laser capture microdissection (LCM), we developed a platform for single-CTC WGS. We performed this procedure on CTCs and tissue samples from a patient with advanced prostate cancer who had serial biopsies over the course of his clinical history. We achieved 30X depth and ≥ 95% coverage. Twenty-nine percent of the somatic single nucleotide variations (SSNVs) identified were founder mutations that were also identified in CTCs. In addition, 86% of the clonal mutations identified in CTCs could be traced back to either the primary or metastatic tumors. In this patient, we identified structural variations (SVs) including an intrachromosomal rearrangement in chr3 and an interchromosomal rearrangement between chr13 and chr15. These rearrangements were shared between tumor tissues and CTCs. At the same time, highly heterogeneous short structural variants were discovered in PTEN, RB1, and BRCA2 in all tumor and CTC samples. Using high-quality WGS on single-CTCs, we identified the shared genomic alterations between CTCs and tumor tissues. This approach yielded insight into the heterogeneity of the mutational landscape of SSNVs and SVs. It may be possible to use this approach to study heterogeneity and characterize the biological evolution of a cancer during the course of its natural history.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9vx810dqTest

المؤلفون: Ando, Tomohiro, Li, Ker-chau

المصدر: The Annals of Statistics, 2017 Dec 01. 45(6), 2654-2679.

الوصول الحر: https://www.jstor.org/stable/26362954Test

المؤلفون: Lee, Pei-Jung, Ho, Chao-Chi, Ho, Hao, Chen, Wan-Jiun, Lin, Chiu-Hua, Lai, Yi-Hua, Juan, Yi-Chen, Chu, Wen-Chung, Lee, Jia-Hua, Su, Sheng-Fang, Chen, Hsuan-Yu, Chen, Jeremy J. W., Chang, Gee-Chen, Li, Ker-Chau, Yang, Pan-Chyr, Chen, Huei-Wen

المصدر: Theranostics ; volume 11, issue 19, page 9667-9686 ; ISSN 1838-7640

الإتاحة: https://doi.org/10.7150/thno.62676Test
https://www.thno.org/v11p9667.htmTest

المؤلفون: Zhou, Kun, Li, Ker-Chau, Zhou, Qing

المساهمون: National Science Foundation

المصدر: Journal of the American Statistical Association ; volume 118, issue 541, page 469-488 ; ISSN 0162-1459 1537-274X

الإتاحة: https://doi.org/10.1080/01621459.2021.1938581Test

المؤلفون: Wu, Ming-Fang, Lin, Chih-An, Yuan, Tzu-Hang, Yeh, Hsiang-Yuan, Su, Sheng-Fang, Guo, Chin-Lin, Chang, Gee-Chen, Li, Ker-Chau, Ho, Chao-Chi, Chen, Huei-Wen

المساهمون: Ministry of Science and Technology, Taiwan, Academia Sinica

المصدر: Cancer Immunology, Immunotherapy ; volume 70, issue 5, page 1435-1450 ; ISSN 0340-7004 1432-0851

مصطلحات موضوعية: Cancer Research, Oncology, Immunology, Immunology and Allergy

الوصف: Background Malignant pleural effusion (MPE)-macrophage (Mφ) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1–M2 transition. The M1/M2 features of MPE-Mφ and their significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear. Methods Total 147 stage-IV lung adenocarcinoma patients undergoing MPE drainage were enrolled for profiling and validation of their M1/M2 spectrum. In addition, the MPE-Mφ signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-Mφ on anti-cancer activity was examined. Results We found that MPE-Mφ expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-Mφ displayed diverse PD-L1 expression patterns, while the low PD-L1 expression group was correlated with higher levels of IL-10. Among these markers, we identified a novel two-gene MPE-Mφ signature, IL-1β and TGF-β1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-Mφ patient cohort ( N = 60, p = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset ( N = 478, p < 0.0001). Significantly, β-glucan worked synergistically with IFN-γ to reverse the risk signature by repolarizing the MPE-Mφ toward the M1 pattern, enhancing anti-cancer activity. Conclusions We identified MPE-Mφ on the M1/M2 spectrum and plasticity and described a two-gene M1/M2 signature that could predict the outcome of late-stage lung cancer patients. In addition, we found that “re-education” of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.

الإتاحة: https://doi.org/10.1007/s00262-020-02781-8Test

المؤلفون: Li, Ker-Chau, Liu, Ching-Ti, Sun, Wei, Yuan, Shinsheng, Yu, Tianwei, Waterman, Michael S.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2004 Nov 01. 101(44), 15561-15566.

الوصول الحر: https://www.jstor.org/stable/3373676Test

المؤلفون: Chen, Chun-Houh, Li, Ker-Chau

المصدر: Lecture Notes-Monograph Series, 2004 Jan 01. 44, 63-86.

الوصول الحر: https://www.jstor.org/stable/4356284Test

المؤلفون: Li, Ker-Chau

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2002 Dec . 99(26), 16875-16880.

الوصول الحر: https://www.jstor.org/stable/3074031Test

المؤلفون: Li, Ker-Chau, Shedden, Kerby

المصدر: Journal of the American Statistical Association, 2002 Sep 01. 97(459), 759-765.

الوصول الحر: https://www.jstor.org/stable/3085719Test