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Genomic profiling of colorectal cancer in large-scale Chinese patients:amplification and somatic mutations in ERBB2

Oncology Research 2024年第9期32卷 1429-1438页

作者： YUZHI LIU EVELYNE BISCHOF ZHIQIN CHEN JIAHUAN ZHOU BEI ZHANG DING ZHANG YONG GAO MING QUAN Department of Oncology Shanghai East HospitalTongji University School of MedicineShanghaiChina State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteDepartment of OncologyRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Jiangsu Hengrui Pharmaceuticals Co. Ltd.ShanghaiChina D Medicines Inc. ShanghaiChina

Objectives:Human epidermal growth factor receptor 2(HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer(mCRC)patients with HER2 amplification,but are not satisfactory in cases of HER2 mutant ***:Consequently,further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2(ERBB2)is *** genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes,tumor mutational burden,microsatellite instability,and programmed death ligand 1(PD-L1)***:Among 2454 CRC patients,85 cases(3.46%)exhibited ERBB2 amplification,and 55 cases(2.24%)carried ERBB2 mutation.p.R678Q(28%),p.V8421(24%),and p.S310F/Y(12%)were the most prevalent of the 16 detected mutation *** comparison to the ERBB2 altered(alt)group,KRAS/BRAF mutations were more prevalent in ERBB2 wild-type(wt)samples(ERBB2wt ***2alt,KRAS:50.9%vs.25.6%,p<0.05;BRAF:8.5%vs.2.3%,p<0.05).32.7%(18/55)of CRCs with ERBB2 mutation exhibited microsatellite instability high(MSI-H),while no cases with HER2 amplification displayed *** genes varied between ERBB2 copy number variation(CNV)and ERBB2 single nucleotide variant(SNV);TP53 alterations tended to co-occur with ERBB2 amplification(92.3%)as opposed to ERBB2 mutation(58.3%).KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases(KRAS/PIK3CA:45.8%/31.2%)compared to ERBB2 amplification cases(KRAS/PIK3CA:14.1%/7.7%).Conclusion:Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from *** findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.

关键词： Colorectal cancer ERBB2 HER2 Human epidermal growth factor receptor 2 genetic profiling Precision oncology

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A Global Approach to Tumor Immunology

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Cellular & Molecular Immunology 2004年第4期1卷 256-265页

作者： EnaWang MonicaCPanelli VladiaMonsurró FrancescoMMarincola Immunogenetics Section Department of Transfusion MedicineClinical CenterNational Institutes of HealthBethesdaMaryland20892USA

Biological and clinical advances in the understanding of tumor immunology suggest that immune responsiveness of human tumors is a complex biological phenomenon that could be best studied by a real-time comparison of tumor/host interactions in the tumor microenvironment through a high-throughput discovery-driven *** conclusion is derived from our recognition that too many hypotheses or,in other words,no solid single hypothesis exist,based on experimental results,to further drive experimentation in human *** genomic studies entertained during the last few years consolidated the belief that in humans the interactions between tumor and immune cells are too complex to be approached exclusively with a hypothesis driven *** believe that immune cells suit cancer cells in a Yin and Yang balance by opposing and yet mutually depending on each ***,immune infiltration in tumors may play a dual role modulating in different circumstances cancer cell growth or destruction through a physiological modulation of *** is reasonable to question what induces inflammation at the tumor *** hypothesize that inflammation is primarily driven by the phenotype of tumor cells that can modulate their microenvironment through cell-to-cell interactions or the secretion of soluble ***,in analogy the observation of immune cells within tumors parallels the presence of paramedics,police and firemen at the scene of an accident,which is reactive to and not causative of the *** this review we will explore this hypothesis by reporting and summarizing most of our recent work in the frame of available literature on the *** & Molecular Immunology.2004;1(4):256-265.

关键词： tumor immunology cDNA arrays genetic profiling vaccination melanoma

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