The <i>p53</i> and <i>mdm</i>‐2 genes in human testicular germ‐cell tumors

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<jats:title>Abstract</jats:title><jats:p>Mutations in the <jats:italic>p53</jats:italic> gene are common in many cancers. They have been documented to occur in about 55% of all cancers of 51 different cell and tissue types. These mutations are accompanied by overexpression of the p53 protein in the nucleus of the cell, and this protein has lost its tumor suppressor function. In this study, 25 testicular germ‐cell (TGC) tumors were tested for <jats:italic>p53</jats:italic> mutations and the level of p53 protein expression. While 67% of the tumors overproduced the p53 protein in the nucleus of 10‐60% of their cells, in all cases the DNA sequence of exons 4‐9 of the <jats:italic>p53</jats:italic> gene was wild type. In this tumor type, there was apparently no selection pressure for <jats:italic>p53</jats:italic> mutations. The <jats:italic>mdm</jats:italic>‐2 gene resides on chromosome 12 (12q13‐q14), a chromosome often altered in TGC tumors. <jats:italic>mdm</jats:italic>‐2 gene amplification (2.5‐ to 10‐fold) was detected in three (12%) of these TGC tumors. These three tumors, and eight additional TGC tumors, overexpressed <jats:italic>mdm</jats:italic>‐2 mRNA. There was a good correlation between overexpression of p53 protein and overexpression of <jats:italic>mdm</jats:italic>‐2 mRNA (<jats:italic>P</jats:italic> = 0.01). This may well result from the fact that the level of <jats:italic>mdm</jats:italic>‐2 mRNA is regulated by the p53 level. These studies demonstrate that TGC tumors fail to be selected for <jats:italic>p53</jats:italic> mutations but nonetheless frequently expressed high levels of wild‐type p53 protein in the cell nucleus. Perhpas this produces the excellent response to radiation and chemotherapy of these tumors, which generally have a good prognosis. Wild‐type p53 may mediate apoptosis in these cells in response to the DNA damage. © 1995 Wiley‐Liss Inc.</jats:p>

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