Neuroblastoma(NB)is one of the most common childhood malignancies.Sixty percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor outcomes.However,the molecular mechanisms trigg...Neuroblastoma(NB)is one of the most common childhood malignancies.Sixty percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor outcomes.However,the molecular mechanisms triggering NB metastasis remain largely uncharacterized.In this study,we generated a transcriptomic atlas of 15447 NB cells from eight NB samples,including paired samples of primary tumors and bone marrow metastases.We used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common‘starter’subpopulation that initiates tumor development and metastasis.The‘starter’population exhibited high expression levels of multiple cell cycle-related genes,indicating the important role of cell cycle upregulation in NB tumor progression.In addition,our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition(p-EMT)along the metastatic route from the primary site to the bone marrow.Our study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis.展开更多
Germline genetic variants,including single-nucleotide variants(SNVs)and copy number variants(CNVs),account for interpatient heterogeneity.In the past several decades,genome-wide association studies(GWAS)have iden-tifi...Germline genetic variants,including single-nucleotide variants(SNVs)and copy number variants(CNVs),account for interpatient heterogeneity.In the past several decades,genome-wide association studies(GWAS)have iden-tified multiple lung cancer-associated SNVs in Caucasian and Chinese populations.These variants either reside within coding regions and change the structure and function of cancer-related proteins or reside within non-coding regions and alter the expression level of cancer-related proteins.The variants can be used not only for cancer risk assessment and prevention but also for the development of new therapies.In this review,we discuss the lung cancer-associated SNVs identified to date,their contributions to lung tumorigenesis and prognosis,and their potential use in predicting prognosis and implementing therapeutic strategies.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81825017,81773034 to Zhe Liu,8217113342,81872350 to Zhenyi Ma)the Ministry of Science and Technology of China(No.2018YFC1313002 to Zhe Liu)+2 种基金the Tianjin Municipal Science and Technology Commission(No.20JCZDJC00110 to Zhe Liu)the Interdisciplinary Research Project of Hangzhou Normal University(No.2024JCXK03 to Zhe Liu)the Haihe Laboratory of Cell Ecosystem Innovation Fund(No.HH22KYZX0025 to Zhe Liu).
文摘Neuroblastoma(NB)is one of the most common childhood malignancies.Sixty percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor outcomes.However,the molecular mechanisms triggering NB metastasis remain largely uncharacterized.In this study,we generated a transcriptomic atlas of 15447 NB cells from eight NB samples,including paired samples of primary tumors and bone marrow metastases.We used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common‘starter’subpopulation that initiates tumor development and metastasis.The‘starter’population exhibited high expression levels of multiple cell cycle-related genes,indicating the important role of cell cycle upregulation in NB tumor progression.In addition,our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition(p-EMT)along the metastatic route from the primary site to the bone marrow.Our study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis.
基金supported by grants from the National Natural Science Foundation of China(Nos.81825017 and 81773034 to Z.L.)the Interdisciplinary Research Project of Hangzhou Normal University(No.2024JCXK03 to Z.L.).
文摘Germline genetic variants,including single-nucleotide variants(SNVs)and copy number variants(CNVs),account for interpatient heterogeneity.In the past several decades,genome-wide association studies(GWAS)have iden-tified multiple lung cancer-associated SNVs in Caucasian and Chinese populations.These variants either reside within coding regions and change the structure and function of cancer-related proteins or reside within non-coding regions and alter the expression level of cancer-related proteins.The variants can be used not only for cancer risk assessment and prevention but also for the development of new therapies.In this review,we discuss the lung cancer-associated SNVs identified to date,their contributions to lung tumorigenesis and prognosis,and their potential use in predicting prognosis and implementing therapeutic strategies.
