Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults
Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults
复制标题
DOI：
10.1158/0008-5472.can-05-0471
复制
发表时间：
2005-09-15
期刊：
影响因子：
11.2
通讯作者：
Shipley, J
中科院分区：
文献类型：
--
作者：
McIntyre, A;Summersgill, B;Shipley, J
我们以前已经确定在4q12扩增在睾丸生殖细胞肿瘤的青少年和成人围绕KIT基因编码的酪氨酸激酶跨膜受体。对190例原发性睾丸生殖细胞肿瘤的分析显示，21%的睾丸生殖细胞瘤亚型的KIT拷贝数增加，而这种变化在非睾丸生殖细胞瘤中很少发现。在大多数情况下，获得的KIT不包括直接侧翼的非编码DNA或侧翼基因KDR和PDGFRA。KIT的拷贝数增加未发现在假定的前体病变，原位癌（CIS），邻近肿瘤的这种变化。KIT过度表达被发现独立的增益和KIT的免疫染色是更强的，在选定的情况下，增益KIT相比，那些没有。结合在13%的腺瘤中鉴定的外显子17中的KIT激活突变，这表明KIT基因产物在CIS向腺瘤的进展中起作用，对其的进一步理解可能导致新的毒性较小的治疗方法。
We have previously identified amplification at 4q12 in testicular germ cell tumors of adolescents and adults centered around the KIT gene encoding a tyrosine kinase transmembrane receptor. Analysis of primary testicular germ cell tumors totaling 190 cases revealed 21% of the seminoma subtype with an increased copy number of KIT whereas this change was rarely found in the nonseminomas. In most cases, gain of KIT did not include the immediately flanking noncoding DNA or the flanking genes KDR and PDGFRA. Increased copy number of KIT was not found in the putative precursor lesion, carcinoma in situ (CIS), adjacent to tumor with this change. KIT overexpression was found independent of gain and KIT immunostaining was stronger in selected cases with gain of KIT compared to those without. Taken together with activating mutations of KIT in exon 17 identified in 13% of seminomas, this suggests that the KIT gene product plays a role in the progression of CIS towards seminoma, the further understanding of which may lead to novel less toxic therapeutic approaches.