1. University of Arizona Cancer Center;
J Cancer. 2013;4(2):104-16. doi: 10.7150/jca.5002. Epub 2013 Jan 10.
Inflammatory breast cancer (IBC) is a rare, highly aggressive form of breast cancer. The mechanism of IBC carcinogenesis remains unknown. We sought to evaluate potential genetic risk factors for IBC and whether or not the IBC cell lines SUM149 and SUM190 demonstrated evidence of viral infection.
We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We evaluated dose-response to treatment with interferon-alpha (IFN-α); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated in IBC) in SUM149 cells. A bioinformatic analysis was performed to evaluate expression of RNase L in IBC and non-IBC.
2 of 2 IBC cell lines were homozygous for RNase L common missense variants 462 and 541; whereas 2 of 10 non-IBC cell lines were homozygous positive for the 462 variant (p= 0.09) and 0 of 10 non-IBC cell lines were homozygous positive for the 541 variant (p = 0.015). Our real-time polymerase chain reaction (RT-PCR) and Southern blot analysis for sequences of HMTV revealed no evidence of the putative viral genome.
We discovered 2 SNPs in the RNase L gene that were homozygously present in IBC cell lines. The 462 variant was absent in non-IBC lines. Our discovery of these SNPs present in IBC cell lines suggests a possible biomarker for risk of IBC. We found no evidence of HMTV in SUM149 cells. A query of a panel of human IBC and non-IBC samples showed no difference in RNase L expression. Further studies of the RNase L 462 and 541 variants in IBC tissues are warranted to validate our in vitro findings.
炎性乳腺癌（IBC）是一种罕见的、侵袭性很强的乳腺癌。IBC 的发病机制尚不清楚。我们试图评估 IBC 的潜在遗传危险因素，以及 IBC 细胞系 SUM149 和 SUM190 是否有病毒感染的证据。
我们对核糖核酸酶（RNase）L 基因的 2 个单核苷酸多态性（SNP）进行了基因分型，这 2 个 SNP 与由于可能的病毒病因而导致的前列腺癌风险相关。我们评估了对干扰素-α（IFN-α）治疗的剂量反应；并在 SUM149 细胞中检测到潜在的人乳腺肿瘤病毒（HMTV，它与 IBC 有关）的证据。进行了生物信息学分析，以评估 RNase L 在 IBC 和非 IBC 中的表达。
2 株 IBC 细胞系均为 RNase L 常见错义突变 462 和 541 的纯合子；而 10 株非 IBC 细胞系中有 2 株为 462 变异的纯合子阳性（p=0.09），10 株非 IBC 细胞系中无 1 株为 541 变异的纯合子阳性（p=0.015）。我们的实时聚合酶链反应（RT-PCR）和 HMTV 序列的 Southern blot 分析未发现潜在病毒基因组的证据。
我们发现 RNase L 基因中的 2 个 SNP 在 IBC 细胞系中纯合存在。462 变异在非 IBC 系中不存在。我们在 IBC 细胞系中发现这些 SNP 的存在表明了 IBC 风险的一个可能的生物标志物。我们在 SUM149 细胞中未发现 HMTV 的证据。对一组人类 IBC 和非 IBC 样本的查询显示，RNase L 的表达没有差异。需要进一步研究 IBC 组织中的 RNase L 462 和 541 变异，以验证我们的体外发现。
