Original Article
Cytogenetic Analyses of 85 Testicular Germ Cell Tumors: Comparison of Postchemotherapy and Untreated Tumors

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Abstract

Cytogenetic analyses of 85 testicular germ cell tumors, of which 54 were karyotypically abnormal, showed recurrent breakpoints at chromosome bands 1p36, 1p13–1qh, 11q23, 19q13, and the pericentromeric regions of the acrocentric chromosomes. Postchemotherapy tumors had significantly more rearrangements of bands 3p25–p26, 6q16–q21, 8p22–p23 when compared with untreated tumors, while untreated tumors had more rearrangements of 9p22–p24 when compared with postchemotherapy tumors. Frequent breakpoints also were identified at 15q15 and 9qh in untreated tumors. Tumors of different histopathology, clinical stage, and treatment status showed no significant differences in the frequencies of i(12p)-positive and i(12p)-negative tumors.

Introduction

The cytogenetic analysis of residual or recurrent testicular germ cell tumors (GCT), those tumors remaining or recurring after therapy, has demonstrated a pattern of cytogenetic abnormalities that is generally similar to that seen in untreated specimens 1, 2, 3, 4. Although early cytogenetic reports differentiated postchemotherapy and untreated specimens in analyses, later reports combined treated and untreated tumors 5, 6, 7, 8, 9, 10, 11, 12. To date, cytogenetic analyses from approximately 81 postchemotherapy specimens have been reported 1, 2, 4, 5, 6, 7, 8, 9, 10, 13, 14. Post-treatment specimens were reported to have more frequent rearrangements of bands 1p36, 6q21, 7q13 (band not in ISCN, 1995 [15]), 10p13 and 12q11–q13 than untreated specimens 8, 16. In a recent study, no differences were identified in chromosomal abnormalities of nonseminomas compared with residual teratomas [4]. Rearrangements of chromosome 12, particularly i(12p), remain the most common chromosomal rearrangement in both untreated and postchemotherapy testicular GCT [16]. Cryptic rearrangements of chromosome arm 12p have been identified in both i(12p)-positive and i(12p)-negative cells derived from untreated testicular GCT [17], suggesting that rearrangements of the short arm of chromosome 12 are common in germ cell tumors.

We report and compare the cytogenetic results of 85 GCT, of which 33 were postchemotherapy (19 were karyotypically abnormal) and the remaining 52 were untreated (35 were karyotypically abnormal). These included both primary tumors and lymph node metastases.

Section snippets

Materials and methods

Eighty-three adult male GCTs were received from patients seen at the Indiana University Medical Center between January 1991 and January 1994. The remaining two tumors were from the Cooperative Human Tissue Network. Thirty-three tumors were postchemotherapy (PC), and 52 were from untreated (UT) patients. Two of the UT tumors (41A and 41B) were from a patient with synchronous, bilateral testicular cancer. Tumor preparation and analysis for cytogenetics, including fluorescence in situ

Results

Fifty-four tumors were karyotypically abnormal, 19 were karyotypically normal, 1 tumor had a constitutional abnormality, and no results were obtained from 11 tumors (10/11 were from patients previously treated with chemotherapy [PC]). The cytogenetic results are given in Table 1, Table 2.

Representative karyotypes from UT tumors are shown in Figure 1 (UT25) and Figure 2 (UT41), and detailed results of all UT tumors are in Table 1, Table 2. In case UT25, the range of chromosome numbers for clone

Discussion

Both acquired and constitutional chromosomal abnormalities have been important in the elucidation of the pathogenesis of some cancers. In solid tumors, many structural rearrangements are frequently present. Some of these rearrangements may be random, while others may be significant for tumor initiation and/or progression. The identification of chromosomal bands that are frequent sites of structural rearrangements in a particular tumor type can be used to indicate the possible locations of genes

Summary

In the current study of 54 cytogenetically abnormal GCT (19 PC and 35 UT), breakpoints at bands 3p25–p26, 6q16–q21, and 8p22–p23 were significantly more common in the PC tumors compared with UT tumors, whereas breakpoints in bands 9p22–p24 were more common in UT tumors compared with PC tumors. Other areas of frequent breakpoints included 1p13–qh, 1p36, 11q23, pericentromeric regions of the acrocentric chromosomes, and 19q13. Frequent breakpoints were observed at 15q15 and 9qh in UT tumors. In

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