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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >How wild-type TP53 is inactivated in undifferentiated-type gastric carcinomas: analyses of intratumoral heterogeneity in deletion and mutation of TP53.
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How wild-type TP53 is inactivated in undifferentiated-type gastric carcinomas: analyses of intratumoral heterogeneity in deletion and mutation of TP53.

机译：野生型TP53如何在未分化型胃癌中失活：TP53缺失和突变的肿瘤内异质性分析。

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OBJECTIVE: In undifferentiated-type gastric carcinoma (UGC), inactivation of TP53 is infrequent at early stages and comparable to tubular adenocarcinomas (TUBs) at advanced stages. To clarify how TP53 inactivation relates to histogenesis of UGCs, we examined p53 alterations in multiple samples of individual UGCs. METHODS: We used 27 UGCs including 12 mixed types with minor tubular component (TC) and 16 with a layered structure (LS), a histological remnant of incipient signet ring cell carcinoma (SIG). We examined p53 expression immunohistochemically and analyzed loss of heterozygosity (LOH) with four microsatellite markers within 17p13.1 in multiple microdissected samples. DNA sequence of mutation hot spots in TP53 was determined in representative samples of each tumor. RESULTS: In the mixed-type UGCs, 5 and 1 of the 8 tumors without LS showed global and regional loss of wild-type TP53, respectively, through mutation and LOH, and one fourth of the tumors with LS showed the regional loss. In the tumors with the mutation, the mutation pattern was identical between TC and poorly differentiated major component. CONCLUSION: The inactivation of wild-type TP53 is an earlier event before dedifferentiation of TUB to mixed-type UGC, but is less frequent and a later event in a subset of mixed-type UGC deriving from SIG. .
机译：目的：在未分化型胃癌（UGC）中，TP53的失活在早期并不常见，与晚期肾小管腺癌（TUB）相当。为了阐明TP53失活如何与UGC的组织发生有关，我们检查了单个UGC的多个样品中的p53改变。方法：我们使用了27种UGC，其中包括12种混合型，其中小管成分（TC）和16种具有分层结构（LS），这是早期印戒细胞癌的组织学残留。我们通过免疫组织化学检查了p53的表达，并在多个显微解剖样本中用17p13.1内的四个微卫星标记分析了杂合性（LOH）的丧失。在每个肿瘤的代表性样品中测定TP53中突变热点的DNA序列。结果：在混合型UGCs中，无LS的8种肿瘤中有5种和1种通过突变和LOH分别显示了野生型TP53的整体和区域性丧失，而具有LS的肿瘤有四分之一显示了区域性丧失。在具有突变的肿瘤中，TC和低分化的主要成分之间的突变模式相同。结论：野生型TP53的失活是在TUB去分化为混合型UGC之前的一个较早事件，但在SIG衍生的混合型UGC的一个子集中，其失活频率较低且较晚。 。

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