Isochromosome 12p in malignant testicular tumors

LETTER TO THE EDITOR Isochromosome 12p in Malignant Testicular Tumors In a recent issue of this journal, Atkin and Baker [1] described an isochromosome for the short arm of chromosome #12 [i(12p)] in at least four seminomas and suggested that this may be a marker specific for malignant testicular tumors. We have i n d e p e n d e n t l y detected an apparently identical marker in several malignant teratomas. Over the past 2 years we have done direct cytogenetic preparations on four seminomas, eight malignant teratomas, and six testicular tumors of mixed histology. In 11 cases, sufficient mitoses and adequate bands were obtained so that the potential presence of markers could be evaluated. An i(12p) was present in four malignant teratomas that had modal chromosome n u m b e r s of 56-62. As described by Atkin and Baker, this is a small metacentric chromosome, similar in size to #19, which cannot be distinguished by C-banding from the F-group chromosomes, except perhaps by its remarkable symmetry. With G-banding, the p r o m i n e n t n e a r l y - m e d i a n dark band on each arm could suggest an isochromosome 21q, but after careful comparison with the #21 long arm, as well as #4, #5, and #12 short arms, we also reached the conclusion that it was an i{12p). Staining of the nucleolar organizing regions in these tumors was uniformative concerning the marker i(12p). In tumor 1, the marker was detected in the majority of cells in a single copy: in tumors 2 and 4, two such marker chromosomes were generally present; and in tumor 3, the i(12p) was present in two to four copies in almsot every cell. This small marker, not present in every metaphase in our studies, is indeed difficult to distinguish if bands are suboptimal. Thus, in some tumors it is difficult to verify its presence or absence. In addition to the i(12p) detected in the four malignant teratomas, we suspect its presence in five other tumors (two seminomas, two malignant teratomas, and one mixed tumor). In two other adequately b a n d e d tumors (one seminoma, one mixed), however, we found no evidence of the marker, though the undetected i n v o l v e m e n t of 12p in other structural rearrangements is, of course, possible. Through trisomy of normal chromosome #12 was often observed in three of the tumors with the i(12p), we did not see higher multiples, as reported by Atkin and Baker; as they studied m a i n l y seminomas, which generally have a higher modal chromosome n u m b e r than do embryonal carcinomas [2], the n u m b e r of extra normal #12 chromosomes is perhaps comparable in the two studies. We did not find excess normal chromosomes #19 and #20 [1], nor have we identified major anomalies of chromosome #1 in any of these 11 tumors. The importance of genes situated on 12p is also apparent from the n u m b e r of copies of the short arm present in these tumor metaphases. It is thus of particular interest that the h u m a n oncogene ras K is located on chromosome #12 [3] and possibly on 12p [4]. An oncogene of the same family, ras N (chromosome #1) has recently been detected in DNA from the h u m a n ovarian teratocarcinoma cell line P A l 15]. Two of the four testicular tumors (tumors 1 and 3) with the i(12p) were first studied after passage as xenografts in the n u d e mouse, and the usefulness of this method of in vivo culture in providing more ample material for study should be

375 "ct 1985 Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017

Cancer Genetics and Gytogenetics 15. 375-376 [19851 0165-4608/85/$03.30

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c . D . D e L o z i e r - B l a n c h e t et al.

p o i n t e d out. T h e use of x e n o g r a f t e d material s h o u l d not h a v e a major effect on the c o n c l u s i o n s , h o w e v e r , as h u m a n t u m o r xenografts g e n e r a l l y m a i n t a i n both the p a t h o l o g i c and c y t o g e n e t i c characteristics of the p a r e n t t u m o r [6]. T h i s was confirmed by the findings in t u m o r 2, in w h i c h surgical a n e d x e n o g r a f t e d s p e c i m e n s gave v i r t u a l l y i d e n t i c a l c y t o g e n e t i c results, w i t h the m a r k e r b e i n g s i m i l a r l y p r e s e n t in both. In a d d i t i o n , in the three different xenograft passages of t u m o r 1 that w e s t u d i e d , the c h r o m o s o m a l m a k e up n e v e r v a r i e d significantly. We thus c o n f i r m the o b s e r v a t i o n by A t k i n and Baker that the i s o c h r o m o s o m e 12p m a y be a significant c y t o g e n e t i c marker present in the m a j o r i t y of m a l i g n a n t germ cell t u m o r s of the testis. The authors would like to thank Dr. J. Costa for providing one of the tumors and Dorothy Pitmon for technical assistance and advice. Supported in part by the Geneva Anti-cancer League and the Krebsliga des Kantons Zurich. C. D A W N D E L O Z I E R - B L A N C H E T ERIC ENGEL HEINRICH W A L T

University Institute of Medical Genetics Geneva, Switzerland Institute of Pathology University of Zurich University Hospital Zurich, Switzerland

REFERENCES 1. Atkin NB, Baker MC (1983): i(12p): Specific chromosomal marker in seminoma and malignant teratoma of the testis? Cancer Genet Cytogenet 10:199-204. 2. Sandberg A (1980): The Chromosomes in Human Cancer and Leukemia. Elsevier, New York, p 512. 3. Sakaguchi AY, Naylor SL, Shows TB, Toole JJ, McCoy M, Weinberg RA (1983): Human cKi-ras 2 proto-oncogene on chromosome 12. Science 219:1081-1082. 4. Gerald PS, Grzeschik KH (1984): Report of the committee on the genetic constitution of chromosomes 10, 11, and 12. Cytogenet Cell Genet 37:103-126. 5. Cooper GM, Blair DG, Oskarsson MK, Tainksy MA, Eader LA, Van de Woude GF (1984): Characterization of human transforming genes from chemically transformed, teratocarcinoma and pancreatic carcinoma cell lines. Cancer Res 44:1-10. 6. Povlsen CO, Visfeldt J, Rygaard J, Jensen G (1975): Growth patterns and chromosomal constitutions of human malignant tumours after long-term serial transplantation in nude nlice. Acta Pathol Microbiol Scand 83:709-716.