Mutations of the p53 gene and p53 protein overexpression are associated with sarcomatoid transformation in renal cell carcinomas.
Mutations of the p53 gene and p53 protein overexpression are associated with sarcomatoid transformation in renal cell carcinomas.
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p53 基因突变和 p53 蛋白过度表达与肾细胞癌中的肉瘤样转化相关。
作者：
Hideaki Oda;Y. Nakatsuru;T. Ishikawa
肾细胞癌有时显示肉瘤样转化，因此包括肉瘤和癌成分。这种肉瘤样肾细胞癌是高度恶性的，具有明显的增殖活性。本调查进行评估的突变状态的p53和H-ras基因独立的癌性和肉瘤部分的个别肿瘤，应用PCR，亚克隆和测序14例。肉瘤样部分显示53基因的极高突变率（11/14，78.6%），在密码子278（8/14，57.1%）和244（6/14，42.9%）处具有两个突变热点。其中5例为双突变，4例为密码子278和244突变，1例为密码子278和248突变。相反，癌性部分显示p53基因的低突变率（2/14，14.3%），未检测到双突变。10例病例显示两种肿瘤成分之间p53基因的遗传异质性。此外，p53过度表达仅在p53突变的那些组分中，主要在肉瘤样部分中被免疫组化观察到。未观察到H-ras突变。这些发现强烈提示p53突变导致p53蛋白过度表达与肾细胞癌肉瘤样转化密切相关。
Renal cell carcinomas sometimes show sarcomatoid transformation, thus comprising both sarcomatous and carcinomatous components. Such sarcomatoid renal cell carcinomas are highly malignant with pronounced proliferative activity. The present investigation was conducted to assess the mutational status of the p53 and H-ras genes independently in carcinomatous and sarcomatous portions of individual tumors, applying PCR, subcloning, and sequencing to 14 cases. Sarcomatoid portions showed an extremely high mutation rate for the 53 gene (11 of 14, 78.6%) with two mutational hot spots at codons 278 (8 of 14, 57.1%) and 244 (6 of 14, 42.9%). Five cases showed double mutations, four cases had mutations at codons 278 and 244, and one case had mutations at codons 278 and 248. In contrast, the carcinomatous portions demonstrated a low mutation rate for the p53 gene (2 of 14, 14.3%) and no double mutations were detected. Ten cases showed genetic heterogeneity in the p53 gene between the two tumor components. Furthermore, p53 overexpression was immunohistochemically observed only in those components with p53 mutations, mainly in the sarcomatoid portions. No H-ras mutations were observed. The findings strongly suggest that p53 mutations leading to overexpression of p53 protein are closely associated with sarcomatoid transformation in renal cell carcinomas.
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肾皮质肿瘤的组织病理学、细胞遗传学和分子特征。
影响因子：
11.2
作者：
PrestiJr,JC;Rao,PH;Chen,Q;Reuter,VE;Li,FP;Fair,WR;Jhanwar,SC
通讯作者：
Jhanwar,SC
影响因子：
56.9
作者：
HOLLSTEIN, M;SIDRANSKY, D;HARRIS, CC
通讯作者：
HARRIS, CC
肿瘤细胞不稳定、多样化和转移表型的进展：从癌基因到癌胎儿表达。
影响因子：
11.2
作者：
Nicolson,GL
通讯作者：
Nicolson,GL
DOI：
10.1073/pnas.88.22.10124
发表时间：
1991-11-01
影响因子：
11.1
作者：
BRASH, DE;RUDOLPH, JA;PONTEN, J
通讯作者：
PONTEN, J
DOI：
10.1073/pnas.90.11.4961
发表时间：
1993-06-01
影响因子：
11.1
作者：
KUPRYJANCZYK, J;THOR, AD;YANDELL, DW
通讯作者：
YANDELL, DW