Molecular cytogenetic analysis of i(12p)-negative human male germ cell tumors

The i(12p) chromosome has been shown to characterize more than 80% of male germ cell tumors (GCTs) and is an important diagnostic marker. Although recent cytogenetic analyses of GCTs have defined nonrandom chromosome abnormalities in these tumors, no attempt has so far been made to compare i(12p)-positive and -negative tumors in terms of their cytogenetic, histologic, and clinical features. During a 5-year period, we have ascertained 202 GCTs, of which 117 had clonally abnormal karyotypes. Among the latter, 91 had one or more copies of i(12p), whereas 26 lacked an i(12p). We report here the karyotypic analysis of these 26 i(12p)-negative GCTs. In this group, nonrandom sites of chromosomal rearrangements included 12p13 (9/26) and 1p11-q11 (5/26). Comparison of the cytogenetic features of i(12p)-negative tumors with i(12p)-positive tumors revealed the only significant difference to be rearrangements affecting 12p13 in the former (35%) as compared to their absence in the latter (3%). Hybridization of metaphase preparations of 9 i(12p)-negative tumors with a chromosome 12 painting probe and with a microdissected 12p painting probe revealed extra copies of chromosome 12 segments incorporated into marker chromosomes whose composition could not otherwise be resolved by banding analysis; all were shown to be derived from 12p. These data demonstrate that both i(12p)-negative and -positive groups are characterized by an increased copy number of 12p, which is consistent with a lack of significant clinical or biological difference between them. An increased 12p copy number thus is a specific aberration of significance to the development of germ cell tumors.