Deletion of the inhibitor of growth 4 (ING4) tumor suppressor gene is prevalent in human epidermal growth factor 2 (HER2)-positive breast cancer.
Deletion of the inhibitor of growth 4 (ING4) tumor suppressor gene is prevalent in human epidermal growth factor 2 (HER2)-positive breast cancer.
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DOI：
10.1016/j.humpath.2010.10.012
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发表时间：
2011-07
期刊：
影响因子：
3.3
通讯作者：
Kim, Suwon
中科院分区：
文献类型：
--
作者：
Tapia, Coya;Zlobec, Inti;Schneider, Sandra;Kilic, Ergin;Gueth, Uwe;Bubendorf, Lukas;Kim, Suwon
生长抑制剂 4 (ING4) 是一种候选抑癌基因，通过阵列比较基因组杂交分析显示，该基因在 10% 至 20% 的乳腺癌中被删除。我们开发了荧光原位杂交技术，可以直接检测肿瘤组织微阵列上组织样本中的 ING4 基因。我们评估了 1033 个乳腺癌组织样本中的 ING4 基因状态，发现 ING4 在所有乳腺癌中有 16.5% (170/1033) 被删除。 ING4 缺失与 Her2 过表达显着相关：在 ING4 缺失的肿瘤中，23.8% (39/164) 为人表皮生长因子 2 (HER2) 阳性，而在没有 ING4 缺失的肿瘤中，这一比例为 14.1% (115/814) (P = .002)。此外，与其他亚型相比，ING4 缺失的肿瘤更有可能属于乳腺癌 HER2 分子亚型（雌激素受体阴性/孕激素受体阴性/人表皮生长因子阳性）（28.4% HER2 vs 15.7%，P = .002）。 ING4 缺失并不影响所有乳腺癌患者 (P = .797) 或 HER2 阳性肿瘤患者 (P = .792) 的生存结果。我们的结论是，ING4 缺失在乳腺癌中相对常见，因为六分之一的乳腺癌存在 ING4 缺失。此外，ING4缺失在HER2阳性肿瘤中更为普遍，表明ING4抑癌基因与HER2癌基因之间存在功能性拮抗关系。这些结果支持了 ING4 是乳腺癌肿瘤抑制因子的观点，并表明 ING4 缺失可能有助于 HER2 阳性乳腺癌的发病机制。
Inhibitor of growth 4 (ING4) is a candidate tumor suppressor gene that was shown to be deleted in 10% to 20% of breast cancers by array comparative genome hybridization analysis. We developed fluorescent in situ hybridization to detect the ING4 gene directly in the tissue samples on tumor tissue microarrays. We evaluated the ING4 gene status in 1033 breast cancer tissue samples and observed that ING4 was deleted in 16.5% (170/1033) of all breast cancers. ING4 deletion was significantly associated with Her2 overexpression: of the tumors with ING4 deletion, 23.8% (39/164) were human epidermal growth factor 2 (HER2) positive, as compared with 14.1% (115/814) of the tumors without ING4 deletion (P = .002). In addition, the tumors with ING4 deletion were more likely to belong to the HER2 molecular subtype (estrogen receptor negative/progesterone receptor negative/human epidermal growth factor positive) of breast cancer, compared with the other subtypes (28.4% HER2 versus 15.7% all, P = .002). ING4 deletion did not affect survival outcome of all patients with breast cancer (P = .797) or of the patients with HER2-positive tumors (P = .792). We conclude that ING4 deletion in breast cancer is relatively common, as 1 in 6 breast cancer harbors ING4 deletion. Furthermore, ING4 deletion is more prevalent in HER2-positive tumors, suggesting a functional antagonistic relationship between the ING4 tumor suppressor and the HER2 oncogene. These results sustain the view that ING4 is a tumor suppressor in breast cancer and suggest that ING4 deletion may contribute to the pathogenesis of HER2-positive breast cancer.
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DOI：
10.1073/pnas.0403621101
发表时间：
2004-07-06
影响因子：
11.1
作者：
Biswas, DK;Shi, Q;Iglehart, JD
通讯作者：
Iglehart, JD
DOI：
10.1073/pnas.0407158101
发表时间：
2004-11-16
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Jain, RK
影响因子：
4.8
作者：
Palacios, Alicia;Munoz, Ines G.;Blanco, Francisco J.
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Blanco, Francisco J.
DOI：
10.1073/pnas.0932692100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Sorlie, T;Tibshirani, R;Botstein, D
通讯作者：
Botstein, D