Adult male germ cell tumors (GCTs) comprise distinct groups: seminomas and nonseminomas, which include pluripotent embryonal carcinomas as well as other histologic subtypes exhibiting various stages of differentiation. Almost all GCTs show 12p gain, but the target genes have not been clearly defined. To identify 12p target genes, we examined Affymetrix (Santa Clara, CA) U133A+B microarray (f83% coverage of 12p genes) expression profiles of 17 seminomas, 84 nonseminoma GCTs, and 5 normal testis samples. Seventy-three genes on 12p were significantly overexpressed, including GLUT3 and REA (overexpressed in all GCTs) and CCND2 and FLJ22028 (overexpressed in all GCTs, except choriocarcinomas). We characterized a 200-kb gene cluster at 12p13.31 that exhibited coordinated overexpression in embryonal carcinomas and seminomas, which included the known stem cell genes NANOG, STELLA, and GDF3 and two previously uncharacterized genes. A search for other coordinately regulated genomic clusters of stem cell genes did not reveal any genomic regions similar to that at 12p13.31. Comparison of embryonal carcinoma with seminomas revealed relative overexpression of several stem cell-associated genes in embryonal carcinoma, including several core ''stemness'' genes (EBAF, TDGF1, and SOX2) and several downstream targets of WNT, NODAL, and FGF signaling (FGF4, NODAL, and ZFP42). Our results indicate that 12p gain is a functionally relevant change leading to activation of proliferation and reestablishment/maintenance of stem cell function through activation of key stem cell genes. Furthermore, the differential expression of core stem cell genes may explain the differences in pluripotency between embryonal carcinomas and seminomas. (Cancer Res 2006; 66(2): 820-7)
ESTICULAR CANCER IS THE MOST common cancer diagnosis in men between the ages of 15 and 35 years, with approximately 8000 cases detected in the United States annually. 1 The majority (95%) of testicular neoplasms are germ cell tumors (GCTs), with other testicular neoplasms (ie, sex-cord stromal tumors, lymphomas) occurring more rarely. Germ cell tumors may also arise in extragonadal locations, such as the mediastinum and retroperitoneum.Remarkable progress has been made in the medical treatment of advanced testicular cancer with a substantial increase in cure rates from approximately 25% in the mid-1970s to nearly 80% today. 2 This cure rate is the highest of any solid tumor and improved survival is primarily due to effective chemotherapy. 3 It is important for all physicians to be familiar with this malignancy, because patients may initially present to a variety of practitioners, and delays in therapy are associated with more extensive disease resulting in more intensive treatment and lower cure rates. 4 In addition, the immediate and longterm toxic effects of treatment often require management from physicians of various disciplines. This article reviews the current evidence-based treatments for advanced testicular GCT, and the acute and chronic toxic effects that may result. The management of early stage (I-IIA) testicular cancers has been reviewed elsewhere. [5][6][7]
BACKGROUND GCT Histology and GeneticsGerm cell tumors are malignancies of primordial germ cells, the cells destined to become spermatozoa. With neoplastic transformation, these cells take on a variety of histologies, reflect-See also Patient Page. CME available online at www.jamaarchivescme.com and questions on p 706.
Four cycles of TIP as second-line therapy achieved a durable CR rate in a high proportion of patients with relapsed testicular GCT. The high CR rate emphasizes the importance of patient selection according to prognostic factors to achieve a favorable outcome to conventional-dose salvage therapy.
The routine inclusion of HDCT in first-line treatment for GCT patients with metastases and a poor predicted outcome to chemotherapy did not improve treatment outcome. Frequent serum marker determinations to estimate marker decline during the first two cycles of BEP chemotherapy provide a clinically useful estimate of outcome.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.