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Study On The Related Factors Of The Origin And Occurrence Of Cardiac Myxoma

Posted on:2021-03-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:J D FanFull Text:PDF
GTID:1484306473469974Subject:Surgery (Cardiothoracic outside)
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Objective:To determine the clonal origin of Cardiac myxoma by analyzing the X chromosome inactivation type of Cardiac myxoma and normal Cardiac tissue by human androgen receptor gene(HUMARA).Through the whole exome sequencing of cardiac myxoma tissues,the SNP analysis and CNV test of cardiac tumors were analyzed to find the SNP sites and CNV events that may play important roles in the occurrence of tumors.Methods: 28 female cardiac myxoma patients were randomly selected.DNA from 28 cardiac myxoma tissues and normal cardiac tissues were extracted,digested by methylated Hhal enzyme,and amplified by polymerase chain reaction(PCR).The product showed polymorphic length by polyacrylamide gel electrophoresis,so as to determine its cloning status.14 tumor tissues of the patients with myxoma(male or female)were randomly selected to SNP analysis and CNV test in gene level through whole exome sequencing.14 samples were divided into two groups according to the size of the tumor in order to find whether there is statistical difference between the two groups.Results: 25 of the 28 cases were heterozygotes,and the heterozygosity rate was89.3%.In the myxoma group,22 specimens showed polyclonal origin,accounting for88%(22/25).In the normal tissue group,24 specimens showed polyclonal origin,accounting for 96%(24/25).There was no significant difference between the two groups,Fisher’s exact probability method P>0.05.The WES results of 14 samples show that 37 cancer-genes were detected,among which 18 mutated sites had a mutation rate of > 10%;and TP53,EP300 and CREBBP played a core binding role in PPI-network.The GO enrichment results showed significant differences in the regulation of cell secretion of the mutated genes,and the KEGG enrichment results showed significant differences in the PI3k-Akt and JAK-STAT signaling pathways in the occurrence of myxoma.In addition,17 new mutation sites of tumor genes with high mutation effect were found in SNP detection.CNV events were also detected in120 tumor genes of the samples,10 of which were included in two tumor databases.The GO enrichment results showed significant differences in the tube development and regulation of cell proliferation,and the KEGG enrichment results showed significant differences in the comprehensive tumor signaling pathway.Two groups were divided according to tumor diameter,significant differences of ercc6 l and ints6 l in CNV test were found through Fisher’s exact probability method(P<0.05).Conclusion:Cardiac myxoma is a multi-cell clonogenic tumor,and it may play a vital role in tumor recurrence.There may be multiple tumor gene site mutations in the process of tumor generation,among which there are multiple core tumor genes such as TP53,EP300 and CREB,which regulate tumor cells through pi3k-akt and jak-stat signaling pathways and play an important role in tumor generation.CNV events were also detected in tumor occurrence,significant differences of ercc6 l and ints6 l in CNV test were found in two groups divided according to tumor diameter,which indicate that the CNV of these two genes may be related to tumor growth.
Keywords/Search Tags:Cardiac myxoma, Clonal origin, X-chromosom, whole genome sequencing, Single nucleotide polymorphism (SNP), Copy number variation (CNV)
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