本文選題：急性淋巴細(xì)胞白血病 + 兒童�。� 參考：《浙江大學(xué)》2016年碩士論文

【摘要】：目的:急性淋巴細(xì)胞白血病(acute lymphoblastic leukemia,ALL)是兒童期最常見的惡性腫瘤,多發(fā)于2-5歲幼兒。雖然ALL的病因及發(fā)病機(jī)制仍不明確,但多認(rèn)為是受遺傳因素和環(huán)境因素的共同影響。我們通過文獻(xiàn)篩選出與歐洲兒童ALL有關(guān)聯(lián)性的 7 個(gè)基因(ARID5B,CDKN2A,CEBPE,IKZF1,INTS10,OR8U8,TP63),并探討這7個(gè)基因的8個(gè)單核苷酸多態(tài)性位點(diǎn)(ARID5B基因rs7089424和rs10994982、CDKN2A 基因 rs3731217、CEBPE 基因 rs4982731、IKZF1 基因rs11978267、INTS10 基因 rs920590、OR8U8 基因 rs1945213、TP63 基因 rs17505102)與中國漢族兒童ALL的關(guān)聯(lián)性,從而有助于進(jìn)一步闡明ALL的發(fā)病機(jī)制。方法:收集我院2015年6月-2015年12月期間入院的190例ALL患兒的血標(biāo)本,提取DNA,并采用PCR結(jié)合質(zhì)譜方法檢測7個(gè)基因(ARID5B、IKZF1、CEBPE、CDKN2A、TP63、OR8U8、INTS10)的 8 個(gè)單核苷酸多態(tài)性位點(diǎn)(rs10994982,rs7089424,rs3731217,rs4982731,rs11978267,rs920590,rs1945213,rs17505102),并以270例非ALL兒童為對照組。之后應(yīng)用統(tǒng)計(jì)學(xué)分析這8個(gè)單核苷酸多態(tài)性位點(diǎn)與兒童ALL相關(guān)性以及同一基因不同基因型與兒童ALL易感性的關(guān)系。結(jié)果:190例ALL患兒中,3-6歲患兒70例(約占36.8%),其中兒童ALL的兩大主要遺傳學(xué)分型-超二倍體(染色體數(shù)目50條)和TEL/AML融合基因,其檢出率分別為18.4%和17.9%。對病例組和正常對照組的8個(gè)單核苷酸多態(tài)性位點(diǎn)的基因頻率及基因型進(jìn)行統(tǒng)計(jì)學(xué)分析,發(fā)現(xiàn)ARID5B基因rs10994982 A風(fēng)險(xiǎn)等位基因和rs7089424 G風(fēng)險(xiǎn)等位基因在病例組和正常對照組之間分布具有統(tǒng)計(jì)學(xué)差異(rs10994982,P=0.003;rs7089424,P=0.001);ARID5B 基因 rs10994982 的基因型AG、AA、GG以及ARID5B基因rs7089424的基因型TT、GG、GT在病例組和正常對照組中的分布具有統(tǒng)計(jì)學(xué)差異(rs10994982,P=0.0014;rs7089424,P=0.0071)。對這8個(gè)單核苷酸多態(tài)性位點(diǎn)與ALL的臨床危險(xiǎn)度、免疫分型以及細(xì)胞遺傳學(xué)分型進(jìn)行統(tǒng)計(jì)學(xué)分析發(fā)現(xiàn),ARID5B基因rs10994982的AA基因型和rs7089424的GT/GG基因型與中國兒童中危組和低危組的ALL有顯著關(guān)聯(lián)性(rs10994982 中危組 OR=2.437,95%CI=1.168-5.085,低危組 OR=3.550,95%CI=1.501-8.397;rs7089424 中危組 OR=1.969,95%CI=1.110-3.495,低危組OR=2.157,95%CI=1.130-4.115),而與高危組沒有關(guān)聯(lián)性。ARID5B 基因 rs10994982 AG/AA基因型和rs7089424GT/GG基因型與兒童B系淋巴細(xì)胞白血病(B-ALL)有關(guān)聯(lián)性,而與兒童T系淋巴細(xì)胞白血病(T-ALL)沒有顯著關(guān)聯(lián)(rs 10994982 B-ALL OR=1.724,95%CI=1.070-2.780,T-ALL OR=1.427,95%CI=0.391-5.204;rs7089424 B-ALL OR=1.841,95%CI= 1.215-2.790,T-ALL OR=0.985,95%CI=0.341-2.846)。ARID5B 基因 rs7089424 的 G 風(fēng)險(xiǎn)等位基因與兒童 B-ALL超二倍體的發(fā)病風(fēng)險(xiǎn)有顯著相關(guān)性(P0.05),ARID5B基因rs10994982的A風(fēng)險(xiǎn)等位基因與兒童ALL的細(xì)胞遺傳學(xué)分型并無明顯的相關(guān)性。CDKN2A基因rs3731217、CEBPE 基因 rs4982731、IKZF1 基因 rs11978267、INTS10 基因 rs920590、OR8U8基因rs1945213和TP63基因rs17505102各自的風(fēng)險(xiǎn)等位基因頻率和基因型頻率在兩組之間的分布結(jié)果均無統(tǒng)計(jì)學(xué)差異。結(jié)論:1、ARID5B基因的單核苷酸多態(tài)性位點(diǎn)rs7089424和rs10994982與兒童ALL易感性有關(guān),同時(shí)也與兒童ALL臨床危險(xiǎn)度分型中的低危組和中危組相關(guān),進(jìn)一步分析發(fā)現(xiàn)這兩個(gè)位點(diǎn)都與兒童B-ALL相關(guān),而與T-ALL沒有關(guān)聯(lián)性。2、未發(fā)現(xiàn) CDKN2A 基因 rs3731217、CEBPE 基因 rs4982731、IKZF1 基因rs11978267、INTS10 基因 rs920590、OR8U8 基因 rs1945213、TP63 基因 rs17505102單核苷酸多態(tài)性位點(diǎn)與中國兒童ALL有關(guān)聯(lián)性。
[Abstract]:Objective: acute lymphoblastic leukemia (ALL) is the most common malignant tumor in childhood, mostly in 2-5 year old children. Although the etiology and pathogenesis of ALL is still not clear, it is considered to be the common influence of genetic and environmental factors. We have screened 7 of the correlation between the ALL and the European children. ARID5B, CDKN2A, CEBPE, IKZF1, INTS10, OR8U8, TP63), and explore the 8 single nucleotide polymorphic loci of these 7 genes (ARID5B gene rs7089424 and rs10994982, CDKN2A gene rs3731217. The association of ALL in children is helpful to further elucidate the pathogenesis of ALL. Methods: the blood samples of 190 ALL children hospitalized in our hospital during the period of December -2015 June 2015 were collected, DNA was extracted, and 8 single nucleotide polymorphisms (ARID5B, IKZF1, CEBPE, CDKN2A, TP63, OR8U8, and OR8U8) were detected by PCR combined mass spectrometry. S10994982, rs7089424, rs3731217, rs4982731, rs11978267, rs920590, rs1945213, rs17505102) and 270 non ALL children as the control group. Then statistical analysis was used to analyze the correlation between the 8 single nucleotide polymorphisms and children ALL, and the relationship between the same gene genotype and the susceptibility to ALL in children. Results: 190 cases of ALL children, 3-6 years old. There were 70 children (about 36.8%), of which two major genetic types of ALL in children were hyper diploid (chromosome number 50) and TEL/AML fusion gene. The detection rates were 18.4% and 17.9%., respectively, for the genetic frequency and genotype of 8 single nucleotide polymorphic loci in the case group and the normal control group, and the ARID5B gene rs109 was found. 94982 A risk alleles and rs7089424 G risk alleles have statistical differences between the case group and the normal control group (rs10994982, P=0.003; rs7089424, P=0.001), and the genotype AG, AA, GG, and the genotype of the ARID5B gene rs10994982 are distributed in the case group and the normal control group. Statistical differences (rs10994982, P=0.0014; rs7089424, P=0.0071). The statistical analysis of the 8 single nucleotide polymorphic loci and the clinical risk, immunophenotype and cell genetic classification of ALL found that the AA genotypes of the ARID5B gene rs10994982 and the GT/GG genotypes of rs7089424 were significant with those of Chinese children's middle and low risk groups and the ALL in the low risk group. Association (rs10994982 medium risk group OR=2.437,95%CI=1.168-5.085, low risk group OR=3.550,95%CI=1.501-8.397; rs7089424 medium risk group OR=1.969,95%CI=1.110-3.495, low risk group OR=2.157,95%CI=1.130-4.115), but not associated with high-risk group.ARID5B gene rs10994982 AG/AA genotype and rs7089424GT/GG genotype and child B lymphatic lymph node Cell leukemia (B-ALL) was associated with T lymphoblastic leukemia (T-ALL) in children (RS 10994982 B-ALL OR=1.724,95%CI=1.070-2.780, T-ALL OR=1.427,95%CI=0.391-5.204; rs7089424 B-ALL OR=1.841,95%CI= 1.215-2.790). There is a significant correlation with the risk of B-ALL hyper diploid in children (P0.05), and there is no significant correlation between the A risk alleles of the ARID5B gene rs10994982 and the cell genetic classification of children ALL,.CDKN2A gene rs3731217, CEBPE gene rs4982731, IKZF1 gene rs11978267, There was no statistical difference in the distribution of the rs17505102 risk allele frequencies and genotype frequencies between the two groups. Conclusion: 1, the single nucleotide polymorphism site rs7089424 and rs10994982 of the ARID5B gene are related to the susceptibility to ALL in children, and also related to the lower and middle risk groups of the children's ALL clinical risk risk classification. The step analysis found that these two loci were all associated with children's B-ALL, but not associated with T-ALL.2, no CDKN2A gene rs3731217, CEBPE gene rs4982731, IKZF1 gene rs11978267, INTS10 gene rs920590, OR8U8 gene polymorphic loci were associated with Chinese children.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R733.71

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相關(guān)期刊論文 前1條

1 鄒堯;劉曉明;張麗;陳玉梅;郭曄;陳曉娟;楊文鈺;王書春;阮敏;劉天峰;張家源;劉芳;戚本泉;竺曉凡;;IKZF1基因拷貝數(shù)異常在兒童BCR/ABL陰性B系急性淋巴細(xì)胞白血病中的意義[J];中國當(dāng)代兒科雜志;2015年11期

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本文編號(hào)：1999975