The ability to identify a specific type of leukemia using minimally invasive biopsies holds great promise to improve the diagnosis,treatment selection,and prognosis prediction of patients.Using genome-wide methylation...The ability to identify a specific type of leukemia using minimally invasive biopsies holds great promise to improve the diagnosis,treatment selection,and prognosis prediction of patients.Using genome-wide methylation profiling and machine learning methods,we investigated the utility of CpG methylation status to differentiate blood from patients with acute lymphocytic leukemia(ALL)or acute myelogenous leukemia(AML)from normal blood.We established a CpG methylation panel that can distinguish ALL and AML blood from normal blood as well as ALL blood from AML blood with high sensitivity and specificity.We then developed a methylation-based survival classifier with 23 CpGs for ALL and 20 CpGs for AML that could successfully divide patients into high-risk and low-risk groups,with significant differences in clinical outcome in each leukemia type.Together,these findings demonstrate that methylation profiles can be highly sensitive and specific in the accurate diagnosis of ALL and AML,with implications for the prediction of prognosis and treatment selection.展开更多
Uveal melanoma is the most common intraocular cancer in the adult eye.R183 and Q209 were found to be mutational hotspots in exon 4 and exon 5 of GNAQ and GNA11 in Caucasians.However,only a few studies have reported so...Uveal melanoma is the most common intraocular cancer in the adult eye.R183 and Q209 were found to be mutational hotspots in exon 4 and exon 5 of GNAQ and GNA11 in Caucasians.However,only a few studies have reported somaticmutations in GNAQ or GNA11 in uveal melanoma in Chinese.We extracted somatic DNA from paraffin-embedded biopsies of 63 Chinese uveal melanoma samples and sequenced the entire coding regions of exons 4 and 5 in GNAQ and GNA11.The results showed that 33%of Chinese uveal melanoma samples carried Q209 mutations while none had R183 mutation in GNAQ or GNA11.In addition,seven novel missense somatic mutations in GNAQ(Y192C,F194L,P170S,D236N,L232F,V230A,and M227I)and four novel missense somatic mutations in GNA11(R166C,I200T,S225F,and V206M)were found in our study.The high mutation frequency of Q209 and the novel missense mutations detected in this study suggest that GNAQ and GNA11 are common targets for somatic mutations in Chinese uveal melanoma.展开更多
基金supported in part by the National Natural Science Foundation of China(Grant 81102248)Science and Technology Plan Projects of Guangdong(Grant 2014A020212695)Natural Science Foundation of Guangdong Province,Major Special Project of Guangzhou Science and Technology and Information Bureau(Grant 122400037)。
文摘The ability to identify a specific type of leukemia using minimally invasive biopsies holds great promise to improve the diagnosis,treatment selection,and prognosis prediction of patients.Using genome-wide methylation profiling and machine learning methods,we investigated the utility of CpG methylation status to differentiate blood from patients with acute lymphocytic leukemia(ALL)or acute myelogenous leukemia(AML)from normal blood.We established a CpG methylation panel that can distinguish ALL and AML blood from normal blood as well as ALL blood from AML blood with high sensitivity and specificity.We then developed a methylation-based survival classifier with 23 CpGs for ALL and 20 CpGs for AML that could successfully divide patients into high-risk and low-risk groups,with significant differences in clinical outcome in each leukemia type.Together,these findings demonstrate that methylation profiles can be highly sensitive and specific in the accurate diagnosis of ALL and AML,with implications for the prediction of prognosis and treatment selection.
基金This work was supported by State Key Laboratory of Ophthalmology(Zhongshan Ophthalmic Center,Sun Yat-Sen University),“100 talents plan”from Sun Yatsen University,the Open Research Funds of the State Key Laboratory of Ophthalmology(2017KF05)Funds of the Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science(2017B030314025)+1 种基金Medical Research Fund of Guangdong Province(No.A2018337)Guangzhou Institute of Pediatrics/GuangzhouWomen and Children’s Medical Center(No.IP-2018-002).
文摘Uveal melanoma is the most common intraocular cancer in the adult eye.R183 and Q209 were found to be mutational hotspots in exon 4 and exon 5 of GNAQ and GNA11 in Caucasians.However,only a few studies have reported somaticmutations in GNAQ or GNA11 in uveal melanoma in Chinese.We extracted somatic DNA from paraffin-embedded biopsies of 63 Chinese uveal melanoma samples and sequenced the entire coding regions of exons 4 and 5 in GNAQ and GNA11.The results showed that 33%of Chinese uveal melanoma samples carried Q209 mutations while none had R183 mutation in GNAQ or GNA11.In addition,seven novel missense somatic mutations in GNAQ(Y192C,F194L,P170S,D236N,L232F,V230A,and M227I)and four novel missense somatic mutations in GNA11(R166C,I200T,S225F,and V206M)were found in our study.The high mutation frequency of Q209 and the novel missense mutations detected in this study suggest that GNAQ and GNA11 are common targets for somatic mutations in Chinese uveal melanoma.
