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首页> 外文期刊>Lung cancer: Journal of the International Association for the Study of Lung Cancer >The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers.
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The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers.

机译:两个单核苷酸多态性3 . 3 H37 / RBM5肿瘤抑制基因与不同亚型的非小细胞肺癌。

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Allele loss and genetic alteration in chromosome 3p, particularly in 3p21.3 region, are the most frequent and the earliest genomic abnormalities found in lung cancer. Multiple 3p21.3 genes exhibit various degrees of tumour suppression activity suggesting that 3p21.3 genes may function as an integrated tumour suppressor region through their diverse biological activities. We have previously demonstrated growth inhibitory effects and tumour suppression mechanism of the H37/RBM5 gene which is one of the 19 genes residing in the 370kb minimal overlap region at 3p21.3. In the current study, in an attempt to find, if any, mutations in the H37 coding region in lung cancer cells, we compared nucleotide sequences of the entire H37 gene in tumour versus adjacent normal tissues from 17 non-small cell lung cancer (NSCLC) patients. No mutations were detected; instead, we found the two silent single nucleotide polymorphisms (SNPs), C1138T and C2185T, within the coding region of the H37 gene. In addition, we found that specific allele types at these SNP positions are correlated with different histological subtypes of NSCLC; tumours containing heterozygous alleles (C+T) at these SNP positions are more likely to be associated with adenocarcinoma (AC), whereas, homozygous alleles (either C or T) are associated with squamous cell carcinoma (SCC) (p=0.0098). We postulate that, these two silent polymorphisms may be in linkage disequilibrium (LD) with a disease causative allele in the 3p21.3 tumour suppressor region which is packed with a large number of important genes affecting lung cancer development. In addition, because of prevalent loss of heterozygosity (LOH) detected at 3p21.3 which precedes lung cancer initiation, these SNPs may be developed into a marker screening for the high risk individuals.
机译:等位基因丢失和染色体的遗传改变3 p,尤其是3 . 3地区,是最频繁和最早的基因异常发现肺癌。表现出不同程度的肿瘤抑制活动说明3 . 3基因可能作为一个集成的肿瘤抑制基因地区通过各自不同的生物活动。生长抑制效果和肿瘤的抑制H37 / RBM5基因的机制之一19基因位于370 kb最小3 . 3重叠。为了找到(如果有的话)的突变在肺癌细胞H37编码区,我们而整个H37的核苷酸序列基因在肿瘤与邻近正常组织从17非小细胞肺癌(NSCLC)病人。发现了两个沉默的单核苷酸多态性,C1138T C2185T,内部H37基因的编码区。我们发现,在这些SNP特定等位基因类型与不同职位相关非小细胞肺癌的组织学亚型;包含在这些杂合的等位基因(C + T)SNP的立场更可能是相关的与腺癌(AC),而纯合子等位基因(C或T)与相关联鳞状细胞癌(SCC) (p = 0.0098)。假设,这两个沉默的多态性可能在连锁不平衡(LD)3 . 3肿瘤疾病病因等位基因抑制区域挤满了一个大的许多重要的基因影响肺癌发展。杂合性丢失(LOH)检测到3 . 3肺癌之前启动,这些单核苷酸多态性可能会发展成一个标记筛查个人风险很高。

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