Samaniego F, Rodriguez E, Houldsworth J, Murty V V, Ladanyi M, Lele K P, Chen Q G, Dmitrovsky E, Geller N L, Reuter V
Laboratory of Cancer Genetics, Sloan-Kettering Institute, New York, New York.
Genes Chromosomes Cancer. 1990 Mar;1(4):289-300. doi: 10.1002/gcc.2870010406.
We report karyotypic analysis of 24 male germ cell tumors (GCTs) with clonally abnormal karyotypes biopsied from testicular and extragonadal lesions from 20 patients belonging to the histologic categories seminoma, teratoma, embryonal carcinoma, choriocarcinoma, and endodermal sinus tumor. Chromosomes 1, 7, 9, 12, 17, 21, 22, and the X chromosome were nonrandomly gained in these tumors. Nonrandom structural changes affected most frequently chromosomes 1 and 12, the latter as i(12p) and/or del(12)(q13----q22). The i(12p) was seen in 90% of tumors which included all histologic subtypes and gonadal as well as extragonadal presentation. Our present results, along with those from published data on fresh GCT biopsies, establish that i(12p) is a highly nonrandom chromosome marker of all histologic as well as anatomic presentations of GCTs. in contrast, we found del(12)(q13----q22) exclusively in nonseminomatous GCTs (NSGCTs) and mixed GCTs (MGCTs) occurring in 44% of such lesions. Because successful cytogenetic analysis of fresh tumor specimens is not always possible, we developed a method based on DNA analysis to detect i(12p) as increased copy number of 12p. In addition to the changes affecting chromosome 12 identified above, we have detected, for the first time, cytological evidence of gene amplification in the form of homogeneously staining regions (HSRs) and double minute chromosomes (dmins) in treated as well as untreated primary extragonadal and metastatic GCTs and confirmed the presence of amplified DNA in one of these tumors at the molecular level by the in-gel renaturation method. Hybridization of DNA from cultured cells from an HSR-bearing tumor with a panel of probes for genes known to be amplified or otherwise perturbed in diverse tumor systems did not identify the amplified gene, suggesting amplification of a novel gene or genes. This study comprises the largest series of GCT cytogenetics attempted so far. Notably, it includes data on a series of primary mediastinal tumors, a group which previously has not been studied in any detail.
我们报告了对24例男性生殖细胞肿瘤（GCT）的核型分析，这些肿瘤具有克隆性异常核型，取自20例患者的睾丸和性腺外病变活检组织，组织学类型包括精原细胞瘤、畸胎瘤、胚胎癌、绒毛膜癌和内胚窦瘤。在这些肿瘤中，1号、7号、9号、12号、17号、21号、22号染色体以及X染色体出现非随机增加。非随机结构改变最常影响1号和12号染色体，后者表现为i(12p)和/或del(12)(q13→q22)。i(12p)见于90%的肿瘤，包括所有组织学亚型以及性腺和性腺外病变。我们目前的结果，连同已发表的新鲜GCT活检数据，证实i(12p)是所有组织学类型以及GCT解剖学表现的高度非随机染色体标志物。相比之下，我们仅在非精原细胞瘤性GCT（NSGCT）和混合性GCT（MGCT）中发现del(12)(q13→q22)，在44%的此类病变中出现。由于并非总能成功对新鲜肿瘤标本进行细胞遗传学分析，我们开发了一种基于DNA分析的方法来检测i(12p)，即12p拷贝数增加。除了上述影响12号染色体的改变外，我们首次在经治疗和未经治疗的原发性性腺外和转移性GCT中检测到以均匀染色区（HSR）和双微体染色体（dmin）形式存在的基因扩增的细胞学证据，并通过凝胶内复性方法在分子水平证实其中一个肿瘤中存在扩增的DNA。用一组已知在不同肿瘤系统中被扩增或其他方式干扰的基因探针，对来自一个携带HSR的肿瘤的培养细胞DNA进行杂交，未鉴定出扩增基因，提示存在一个或多个新基因的扩增。本研究是迄今为止尝试的最大系列GCT细胞遗传学研究。值得注意的是，它包括了一系列原发性纵隔肿瘤的数据，这组肿瘤此前尚未进行过详细研究。
