No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis

Abstract

Malignant transformation may be caused by gene deregulation resulting from specific chromosomal rearrangements, by amplification, by mutations in proto-oncogenes, by loss of tumor suppressor genes, or a combination of these. We investigated the role of numerical and structural chromosomal abnormalities in 102 cytogenetically abnormal cases of primary testicular germ cell tumors of adolescents and adults (TGCT) [32 seminomas (SE) and 70 nonseminomatous germ cell tumors (NS)]. We confirmed that an isochromosome for 12p, i(12p), is the only consistent structural chromosomal abnormality in TGCT, present in about 70% of our cases. Both the frequency and the number of copies of i(12p) are higher in NS than in SE. This may suggest that i(12p) is involved in tumor progression. Besides i(12p), several clonal structural chromosomal abnormalities were found, but none appeared to be specific. SE and NS had chromosome numbers in the triploid range, with significantly higher numbers in SE than in NS (average modal chromosome numbers of 73.4 in SE and 65.0 in NS). Both in SE and NS, some chromosomes were significantly underrepresented (e.g., 11, 13, 18, and Y) and others overrepresented (e.g., 7, 8, 12, 21, and X). In SE, a significantly higher copy number of chromosomes 7, 15, 19, and 22 was found and a significantly lower number of chromosome 17, compared with NS. These chromosomes may play an important role in the differentiation of TGCT.

Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults

“…The fact that the presence of the cyclin D2 in NS depends on the histology (Houldsworth et al, 1997) is neutral with respect to the hypothesis that cyclin D2 is the gene of interest. Overrepresentation of the cyclin D2 gene in most of the TGCTs and derived cell lines (Sicinski et al, 1996) probably merely re¯ects the over-representation of the complete short arm of chromosome 12 found in virtually all TGCTs (Mukherjee et al, 1991;Rodriquez et al, 1993a,b;Van Echten et al, 1995;Mostert et al, 1996b). A number of other genes previously proposed as candidates we also considered less likely because they map outside the SROA (Table 1).…”

“…It has been known for more than a decade that the majority of TGCTs contains one or more isochromosomes of the short arm of chromosome 12 (Mukherjee et al, 1991;Rodriquez et al, 1993a;Van Echten et al, 1995;Mostert et al, 1996b). Moreover, it has been demonstrated, that TGCTs without i(12p) also show over-representation of 12p-sequences (Suijkerbuijk et al, 1993;Rodriquez et al, 1993b;Smolarek et al, 1995).…”

“…Both types of TGCTs originate from a common precursor, known as carcinoma in situ (Skakkebñk et al, 1987) or intratubular germ cell neoplasia (Stamp and Jacobsen, 1995). A large number of TGCTs, both primary and metastatic, of various histologies have been studied for their chromosomal constitution by di erent investigators, including ourselves (Rodriquez et al, 1993a;Van Echten et al, 1995;Sandberg et al, 1996, for review). Besides non-random patterns of over-and underrepresentation of (parts of) chromosomes, gain of 12p is a consistent ®nding.…”

Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization

“…However, these are less frequent and less consistent as compared to gain of 12p. [10][11][12] Notably, testicular germ cell tumors that arise during infancy and childhood show a divergent genetic profile that is characterized by loss of 1p and 6q, and gain of 1q and 20, while gain of 12p11-12 is not detectable. [13][14][15][16] In extragonadal germ cell tumors, similar age-dependent cytogenetic and moleculargenetic patterns have been identified.…”

Reviews of Chromosome Studies in Urological Tumors. III. Cytogenetics and Genes in Testicular Tumors

“…Rodriguez et al 32 [48][49][50][51][52][53], XY, add(l)(p36), +der(l;3)(ql0;ql0), add(5)(q35), +7, +der(9)t(9;12)(pl3;ql3), del(10)(q24), -18, -19, +20, +der(?)t(? ;q21), + m arl, +mar2, +mar3, +mar4, +2mar 50-56, XXY, del(l)(p35), -2 , -3 , -4 , -5 , der(6)t(6;15)(qll;qll), del(7)(qll), -8 , -9 , -10, -11, -12, i(12)(pl0)x2, - , ine 69, XXY, del(l)(q31), i(12p), t(2;16)(q33;pl3), t(9;20)(p23;pl2), t(22;?)(ql3;?)…”