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2016年3月24日讯 /生物谷BIOON/ –最近，来自美国奥古斯塔大学佐治亚医学院病理系的研究人员发现GT198基因突变或可成为乳腺癌早期诊断和治疗的新靶向目标。
早先研究发现该基因发生的突变主要出现在早发乳腺癌和卵巢癌。现在科学家们证明帮助形成健康乳腺组织的干细胞或祖细胞也会存在GT198基因突变，并为乳腺癌的发生提供一个绝佳的“温床”。
相关研究结果发表在国际学术期刊American Journal of Pathology上，该研究共包含254例绝经前和绝经后的乳腺癌患者。
文章通讯作者Dr. Lan Ko这样说道：“该基因突变可能存在于病人的血液和肿瘤组织，在肿瘤组织中的比例非常高。我们认为该基因一旦发生突变，就会诱导肿瘤生长。”
GT198在正常情况下会受到雌激素调控，同时也是类固醇激素受体比如雌激素受体的一个共激活因子。该基因发生突变后，GT198就能够在没有雌激素的情况下促进肿瘤生长。
科学家们已经发现在癌化的乳腺组织中GT198基因突变存在于多种细胞类型，其中包含脂肪细胞，成纤维细胞，血管周围细胞以及肌上皮细胞等类型，但是为何会发生这种情况一直没有得到很好的解释。该研究为解答该问题提供了一些线索，他们发现突变的GT198能够直接影响血管周围的乳腺干细胞，而这些干细胞是形成乳腺组织不同细胞成分的来源。
文章另外一位共同作者Dr. Nita Maihle表示，这项研究证明了之所以不同类型的乳腺基质细胞都会受到GT198基因突变的影响可能是因为它们都来源于携带GT198基因突变的干（祖）细胞，为乳腺癌的发生发展提供了一个很好的肿瘤形成微环境。这项研究为乳腺癌的诊断治疗找到了一个新的潜在靶点，下一步他们将继续寻找治疗方法纠正发生了“错误”的干（祖）细胞。（基因宝jiyinbao.com）
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doi:10.1016/j.ajpath.2016.01.006
GT198 Expression Defines Mutant Tumor Stroma in Human Breast Cancer
Zheqiong Yang∗, Min Peng∗, †, Liang Cheng‡, Kimya Jones§, Nita J. Maihle∗, ¶, ‖, Nahid F. Mivechi∗, Lan Ko∗, §
Human breast cancer precursor cells remain to be elucidated. Using breast cancer gene product GT198 (PSMC3IP; alias TBPIP or Hop2) as a unique marker, we revealed the cellular identities of GT198 mutant cells in human breast tumor stroma. GT198 is a steroid hormone receptor coactivator and a crucial factor in DNA repair. Germline mutations in GT198 are present in breast and ovarian cancer families. Somatic mutations in GT198 are present in ovarian tumor stromal cells. Herein, we show that human breast tumor stromal cells carry GT198 somatic mutations and express cytoplasmic GT198 protein. GT198+ stromal cells share vascular smooth muscle cell origin, including myoepithelial cells, adipocytes, capillary pericytes, and stromal fibroblasts. Frequent GT198 mutations are associated with GT198+ tumor stroma but not with GT198− tumor cells. GT198+ progenitor cells are mostly capillary pericytes. When tested in cultured cells, mutant GT198 induces vascular endothelial growth factor promoter, and potentially promotes angiogenesis and adipogenesis. Our results suggest that multiple lineages of breast tumor stromal cells are mutated in GT198. These findings imply the presence of mutant progenitors, whereas their descendants, carrying the same GT198 mutations, are collectively responsible for forming breast tumor microenvironment. GT198 expression is, therefore, a specific marker of mutant breast tumor stroma and has the potential to facilitate diagnosis and targeted treatment of human breast cancer.