We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analy...We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analysis of the complementarity-determinining region III (CDR III) of the immunoglobulin heavy chain genes showed identical gene rearrangements in the CLL- and the MM-cell population. Our findings prove a common clonal tumor origin of both B-cell diseases in this patient.展开更多
Objective: Multiple mechanisms underlying the development of portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) have been reported recently. However, the origins of PVTT remain unknown. Increasing multi...Objective: Multiple mechanisms underlying the development of portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) have been reported recently. However, the origins of PVTT remain unknown. Increasing multi-omics data on PVTTs in HCCs have made it possible to investigate whether PVTTs originate from the corresponding primary tumors(Ts).Methods: The clonal relationship between PVTTs and their corresponding primary Ts was investigated using datasets deposited in public databases. One DNA copy number variations dataset and three gene expression datasets were downloaded for the analyses.Clonality analysis was performed to investigate the clonal relationship between PVTTs and Ts from an individual patient.Differential gene expression analysis was applied to investigate the gene expression profiles of PVTTs and Ts.Results: One out of 19 PVTTs had no clonal relationship with its corresponding T, whereas the others did. The PVTTs with independent clonal origin showed different gene expression and enrichment in biological processes from the primary Ts. Based on the unique gene expression profiles, a gene signature including 24 genes was used to identify pairs of PVTTs and primary Ts without any clonal relationship. Validation in three datasets showed that these types of pairs of PVTTs and Ts can be identified by the 24-gene signature.Conclusions: Our findings show a direct evidence for PVTT origin and consolidate the heterogeneity of PVTTs observed in clinic.The results suggest that PVTT investigation at a molecular level is clinically necessary for diagnosis and treatment.展开更多
Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its cellular origin rem...Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its cellular origin remains unclear.The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC.Methods:The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC(5HC).Loss of heterozygosity(LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC.Expression of hepatocyte markers[hepatocyte paraffin 1(Hep Par 1) and glypican 3(GPC3)]and cholangiocyte markers[cytokeratin(CK)7 and 19]in tumor tissues was examined by immuno histochemical analysis.Results:In the 16 CHC specimens,the difference in LOH patterns between HCC and ICC was less than 30%,suggesting the same clonal origin of HCC and ICC.Consistent with this finding,immunohistochemical analysis revealed that hepatocyte markers(Hep Par 1 and GPC3) and cholangiocyte markers(CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9%of CHC specimens,suggesting that the two components shared a similar phenotype with hepatic progenitor cells(HPCs).On the contrary,in all 10 SHC cases,the difference in LOH patterns between the HCC and ICC components was greater than 30%,suggesting different clonal origins of HCC and ICC.Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC(P < 0.05).Conclusions:Our results suggest that the HCC and ICC components of CHC may originate from the same clone,having the potential for dual-directional differentiation similar to HPCs.CHC tended to exhibit the biological behaviors of both HCC and ICC,which may enhance the infiltrative capacity of tumor cells,leading to poor clinical outcomes for patients with CHC.展开更多
1文献来源
[1] Wang X, Wang M, Maclennan GT, et al. Evidence for common clonal origin of muhifocal lung cancers. [J]. J Natl Cancer Inst,2009,101 （8） ：560- 570.
文摘We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analysis of the complementarity-determinining region III (CDR III) of the immunoglobulin heavy chain genes showed identical gene rearrangements in the CLL- and the MM-cell population. Our findings prove a common clonal tumor origin of both B-cell diseases in this patient.
基金supported by grants of China National Funds for Distinguished Young Scientists (Grant No. 81425019)National Natural Science Foundation of China (Grant No. 81672899)+2 种基金the State Key Program of National Natural Science Foundation of China (Grant No. 81730076)Shanghai Science and Technology Committee Program (Grant No. 18XD1405300)Specially-Appointed Professor Fund of Shanghai (Grant No. GZ2015009)
文摘Objective: Multiple mechanisms underlying the development of portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) have been reported recently. However, the origins of PVTT remain unknown. Increasing multi-omics data on PVTTs in HCCs have made it possible to investigate whether PVTTs originate from the corresponding primary tumors(Ts).Methods: The clonal relationship between PVTTs and their corresponding primary Ts was investigated using datasets deposited in public databases. One DNA copy number variations dataset and three gene expression datasets were downloaded for the analyses.Clonality analysis was performed to investigate the clonal relationship between PVTTs and Ts from an individual patient.Differential gene expression analysis was applied to investigate the gene expression profiles of PVTTs and Ts.Results: One out of 19 PVTTs had no clonal relationship with its corresponding T, whereas the others did. The PVTTs with independent clonal origin showed different gene expression and enrichment in biological processes from the primary Ts. Based on the unique gene expression profiles, a gene signature including 24 genes was used to identify pairs of PVTTs and primary Ts without any clonal relationship. Validation in three datasets showed that these types of pairs of PVTTs and Ts can be identified by the 24-gene signature.Conclusions: Our findings show a direct evidence for PVTT origin and consolidate the heterogeneity of PVTTs observed in clinic.The results suggest that PVTT investigation at a molecular level is clinically necessary for diagnosis and treatment.
基金supported by the grants from the National Natural Science Foundation of China(Nos.81072026 and 81272662)the Science Fund for Creative Research Groups of China(No.81221061)the Key Project of Science and Technology Committee of Shanghai(No.10411951000)
文摘Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its cellular origin remains unclear.The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC.Methods:The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC(5HC).Loss of heterozygosity(LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC.Expression of hepatocyte markers[hepatocyte paraffin 1(Hep Par 1) and glypican 3(GPC3)]and cholangiocyte markers[cytokeratin(CK)7 and 19]in tumor tissues was examined by immuno histochemical analysis.Results:In the 16 CHC specimens,the difference in LOH patterns between HCC and ICC was less than 30%,suggesting the same clonal origin of HCC and ICC.Consistent with this finding,immunohistochemical analysis revealed that hepatocyte markers(Hep Par 1 and GPC3) and cholangiocyte markers(CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9%of CHC specimens,suggesting that the two components shared a similar phenotype with hepatic progenitor cells(HPCs).On the contrary,in all 10 SHC cases,the difference in LOH patterns between the HCC and ICC components was greater than 30%,suggesting different clonal origins of HCC and ICC.Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC(P < 0.05).Conclusions:Our results suggest that the HCC and ICC components of CHC may originate from the same clone,having the potential for dual-directional differentiation similar to HPCs.CHC tended to exhibit the biological behaviors of both HCC and ICC,which may enhance the infiltrative capacity of tumor cells,leading to poor clinical outcomes for patients with CHC.
文摘1文献来源
[1] Wang X, Wang M, Maclennan GT, et al. Evidence for common clonal origin of muhifocal lung cancers. [J]. J Natl Cancer Inst,2009,101 （8） ：560- 570.
