APOBEC3B high expression status is associated with aggressive phenotype in Japanese breast cancers

APOBEC3B high expression status is associated with aggressive phenotype in Japanese breast cancers
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DOI:
10.1007/s12282-015-0641-8
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发表时间:
2016-09-01
期刊:
影响因子:
4
通讯作者:
Nishiyama, Masahiko
Nishiyama, Masahiko
中科院分区:
医学3区
文献类型:
--
作者:
Tsuboi, Miki;Yamane, Arito;Nishiyama, Masahiko

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AID/APOBEC蛋白家族成员具有胞苷脱氨酶活性,可将DNA和RNA上的胞苷残基转化为尿苷。最近的研究表明,APOBEC 3B(A3 B)可能是乳腺癌基因组的DNA突变体。采用实时定量RT-PCR对93例原发性乳腺癌组织(74例雌激素受体(ER)阳性,3例ER和HER 2阳性,6例HER 2阳性,10例三阴性)(包括37对肿瘤-正常组织)的A3 B mRNA表达进行了评估。分析A3 B基因表达、TP 53和PIK 3CA直接测序突变分析、A3 B基因多态性缺失等位基因与人乳头瘤病毒(HPV)感染的关系。A3 B高表达与淋巴结转移的亚型、进展及病理核分级有关。A3 B在乳腺癌组织中的表达高于癌旁组织,且与乳腺癌的淋巴结转移和细胞核分级有关,而淋巴结转移和细胞核分级是乳腺癌侵袭性的可靠表型标志。A3 B在乳腺癌组织中的表达可作为乳腺癌恶性潜能的标志物。
The members of AID/APOBEC protein family possess cytidine deaminase activity that converts cytidine residue to uridine on DNA and RNA. Recent studies have shown the possible influence of APOBEC3B (A3B) as DNA mutators of breast cancer genome. However, the clinical significance of A3B expression in Japanese breast cancer has not been studied in detail.Ninety-three primary breast cancer tissues (74 estrogen-receptor (ER) positive, 3 ER and HER2 positive, 6 HER2 positive, and 10 triple negative) including 37 tumor-normal pairs were assessed for A3B mRNA expression using quantitative real-time RT-PCR. We analyzed the relation between A3B expression, mutation analysis of TP53 and PIK3CA by direct sequencing, polymorphic A3B deletion allele and human papillomavirus (HPV) infection in tumors.A3B mRNA was overexpressed in tumors compared with normal tissue. Patients with high A3B expression were associated with subtype and progression of lymph node metastasis and pathological nuclear grade. However, the expression was not related to any other clinicopathological factors, including mutation of TP53 and PIK3CA, polymorphic A3B deletion allele, HPV infection and survival time.The expression of A3B in breast cancer was higher than in non-cancerous tissues and was related to the lymph node metastasis and nuclear grade, which are reliable aggressive phenotype markers in breast cancer. Evaluation of A3B expression in tumor may be a marker for breast cancer with malignant potential.