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埃及乳腺癌患者中FHIT基因纯合缺失的多种模式

Multiple Patterns of FHIT Gene Homozygous Deletion in Egyptian Breast Cancer Patients.

作者信息

Ismail Heba M S, Medhat Amina M, Karim Amr M, Zakhary Nadia I

机构信息

Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

Int J Breast Cancer. 2011;2011:325947. doi: 10.4061/2011/325947. Epub 2011 Oct 19.

Abstract

Fragile histidine triad (FHIT) gene encodes a putative tumour suppressor protein. Loss of Fhit protein in cancer is attributed to different genetic alterations that affect the FHIT gene structure. In this study, we investigated the pattern of homozygous deletion that target the FHIT gene exons 3 to 9 genomic structure in Egyptian breast cancer patients. We have found that 65% (40 out of 62) of the cases exhibited homozygous deletion in at least one FHIT exon. The incidence of homozygous deletion was not associated with patients' clinicopathological parameters including patients' age, tumour grade, tumour type, and lymph node involvement. Using correlation analysis, we have observed a strong correlation between homozygous deletions of exon 3 and exon 4 (P < 0.0001). Deletions in exon 5 were positively correlated with deletions in exon 7 (P < 0.0001), Exon 8 (P < 0.027), and exon 9 (P = 0.04). Additionally, a strong correlation was observed between exons 8 and exon 9 (P < 0.0001).We conclude that FHIT gene exons are homozygously deleted at high frequency in Egyptian women population diagnosed with breast cancer. Three different patterns of homozygous deletion were observed in this population indicating different mechanisms of targeting FHIT gene genomic structure.

摘要

脆性组氨酸三联体(FHIT)基因编码一种假定的肿瘤抑制蛋白。癌症中Fhit蛋白的缺失归因于影响FHIT基因结构的不同基因改变。在本研究中,我们调查了埃及乳腺癌患者中靶向FHIT基因外显子3至9基因组结构的纯合缺失模式。我们发现65%(62例中的40例)的病例在至少一个FHIT外显子中表现出纯合缺失。纯合缺失的发生率与患者的临床病理参数无关,包括患者年龄、肿瘤分级、肿瘤类型和淋巴结受累情况。通过相关性分析,我们观察到外显子3和外显子4的纯合缺失之间存在强相关性(P < 0.0001)。外显子5的缺失与外显子7的缺失呈正相关(P < 0.0001)、外显子8(P < 0.027)和外显子9(P = 0.04)。此外,在外显子8和外显子9之间观察到强相关性(P < 0.0001)。我们得出结论,在被诊断为乳腺癌的埃及女性人群中,FHIT基因外显子高频发生纯合缺失。在该人群中观察到三种不同的纯合缺失模式,表明靶向FHIT基因基因组结构的不同机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e2f/3262564/63f116e7cb74/IJBC2011-325947.001.jpg

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