Testicular Germ Cell Tumor 1

For a general phenotypic description and a discussion of genetic heterogeneity of testicular germ cell tumors, see 273300.

Mapping

Rapley et al. (2000) analyzed the X chromosome in 99 families with testicular germ cell tumor compatible with X linkage, 80% of which were sib pairs, and found preliminary evidence for a TGCT predisposition locus at Xq27-q28 (hlod score, 2.01). Stratification analysis showed that families with at least 1 case of bilateral disease showed strong evidence of linkage to the Xq27 locus, with an hlod score of 4.76 (genomewide p = 0.034). The proportion of families with undescended testis linked to this locus was 73% compared with 26% of families without undescended testis. These results provided evidence for a TGCT susceptibility gene on Xq27 that may also predispose to undescended testis. Rapley et al. (2000) stated that TGCT1 was the first cancer susceptibility gene to be mapped in a genomewide search predominantly using sib pairs and the third cancer-predisposing gene to be mapped to the X chromosome, the others being the prostate cancer susceptibility gene (HPCX; 300147) and the androgen receptor gene (AR; 313700), mutations in which are associated with familial male breast cancer.

Molecular Genetics

TGCT Locus and Klinefelter Syndrome

Rapley et al. (2000) pointed out that Klinefelter syndrome (47,XXY) is a risk factor for extragonadal germ cell tumors. The relative risk of mediastinal germ cell tumors in Klinefelter syndrome is 67 (Hasle et al., 1995), and 8% of males with mediastinal germ cell tumors have Klinefelter syndrome (Hasle et al., 1992). This raised the possibility that 2 active normal copies of a putative TGCT1 gene may be responsible for the increased risk of germ cell tumors in Klinefelter syndrome.