Correlation of Chromosome Abnormalities with Histolã³gica! and Clinical Features in Wilms' and Other Childhood Renal Tumors1

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[CANCER RESEARCH 51. 5937-5942, November 1. 1991] Correlation of Chromosome Abnormalities with HistolÃ³gica! and Clinical Features in Wilms' and Other Childhood Renal Tumors1

Yasuhiko Kaneko,2 Chieko Homma, Nobuo Maseki, Masaharu Sakurai, and Jun-ichi Hata Department of Laboratory Medicine [Y. A'., C. H.] and Hematotogy Clinic [N. M., M. S./, Saitama Cancer Center Hospital, Ina, Saitama 362, Japan, and Department of Pathology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160, Japan [J. H.j

ABSTRACT childhood renal tumors. Our findings and a review of data on other Wilms' tumors (14-19) suggest that increased copy num Chromosomes and histology were successfully studied in 33 childhood ber of genes on the nonrandomly gained chromosomes might renal tumors. Thirty-one tumors were classified as one of four subtypes contribute to the genesis of many Wilms1 tumors and that of Wilms1 tumor. Of 24 typical Wilms' tumors, 12 had hyperdiploidy with nonrandom trisomies, mostly including +6 and/or +12. Three typical deletion of various tumor suppressor genes other than WTl Wilms1 tumors with an Hpl3 deletion or a pericentric inversion with a might also play a critical role in the development of some break in 11pi3 were not associated with aniridia. Two other typical tumors. In addition, we compared chromosome patterns be Wilms1 tumors with the Hpl3 deletion and one fetal rhabdomyomatous tween Japanese Wilms1 tumors and American and British ones, nephroblastoma with an Hpl3 translocation were associated with aniri to clarify whether the higher incidence in Caucasian children is dia. Two cystic partially differentiated nephroblastomas showed hyper related to the predominance of Wilms1 tumor with specific diploidy with +12. Of four clear cell sarcomas of the kidney, three had chromosome abnormalities. normal diploidy and the other had a 2:22 translocation. Two congenital mesoblastic nephromas had hyperdiploid karyotype with trisomy 11, which was never seen in the 31 Wilms1 tumors. Our findings and a review MATERIALS AND METHODS of data on 102 reported Wilms1 tumors revealed Ilpl3 abnormalities in Patients. Chromosomes and histology were studied in renal tumors 24 tumors, HplS abnormalities in five tumors, and partial deletions of from 40 Japanese infants and children who were consecutively admitted Ip, 7p, I Iq. 12q, 16q, or 17p or monosomy of No. 21 or No. 22 each in to various institutions (listed in "Acknowledgments'1) between Novem four or more tumors. ber 1982 and April 1990. The tumor tissues from 38 patients were These findings suggest that increased copy number of genes on the obtained by surgery and were transferred to the cytogenetic laboratory nonrandom trisomie chromosomes might contribute to the genesis of many Wilm's tumors and that deletion of various tumor suppressor genes of the Saitama Cancer Center Hospital. One cell line and two xenografts other than a Wilms' tumor gene, WTl in 1Ipl3, might also play a critical established from untreated primary tumors by Dr. Yoshiro Yamashita, Niigata University, and Dr. Yoshiaki Tsuchida, National Children's role in the development of some tumors. Hospital, respectively, were also studied. One tumor (No. 12), from which one of the two xenografts was established, was included in the 38 tumors. Patients were staged according to the National Wilms1 INTRODUCTION Tumor Study staging system and were treated with the National Wilms1 Some chromosome abnormalities found in constitutional Tumor Study protocol on the basis of their stage (20). Three patients were diagnosed as having AWTA3 (2). cells as well as tumor cells play an essential role in locating genes involved in the pathogenesis of cancers (1). An 11pi3 HistolÃ³gica!Studies. The pathological diagnosis was made on routine deletion found in constitutional cells of Wilms1 tumor-aniridia- hematoxylin/eosin-stained slides, which were prepared from primary tumors obtained before chemotherapy or radiotherapy. The tumors genito-urinary abnormalities-mental retardation syndrome pa were classified as one of four subtypes of Wilms' tumor or as congenital tients (2) and in tumor cells of sporadic Wilms1 tumor patients mesoblastic nephroma. Typical Wilms1 tumor shows triphasic compo (3) suggested the position of one Wilms1 tumor gene. The nents of epithelial, blastema!, and mesenchymal tissue, without any proposition was further substantiated by the findings of allelic anaplastia changes (21). Fetal rhabdomyomatous nephroblastoma is a loss of the 11p 13 region, determined by restriction fragment monophasic mesenchymal variant of Wilms' tumor with differentiated length polymorphism analysis (4-6), and finally led to the striated muscle cells (22). Cystic partially differentiated nephroblastoma cloning of the WTl gene (7, 8). is a cystic encapsulated tumor with septal wall composed of flattened In some Wilms1 tumors, however, allelic loss was found only epithelial lining, underyling cellular stroma, rhabdomyomatous cells, and other foci resembling typical Wilms' tumor and occurs before 2 in the 11pi5 region and not in the 11p 13 region (9, 10). years of age (23). Clear cell sarcoma of the kidney shows a diffuse Furthermore, linkage studies showed no association between some familial Wilms' tumor patients and DNA markers local proliferation of water clear cells with round normochromatic nuclei (24). It is controversial whether the sarcoma is considered to be a ized in either Ilpl3 or HplS (11, 12). These findings suggest variant of Wilms' tumor (24, 25). Congenital mesoblastic nephroma the presence of at least two other Wilms1 tumor genes, one at shows a varied cellular growth of spindle cells and is considered to be 11p 15 and the other somewhere other than Ilpl3 or 11p 15. a benign tumor of infancy (26). Another interesting aspect of Wilms1 tumor is its markedly Chromosome Studies. The tumor tissue was minced with scissors, different incidences between East Asian and Caucasian children disaggregated in 0.8% collagenase type II (Worthington) in RPMI 1640 (13); the latter suffer from the tumor 2 to 3 times more for 3 h, and cultured in plastic dishes containing ES medium (Nissui frequently than the former. Seiyaku, Tokyo, Japan) with 15% fetal calf serum. The cells were We studied chromosomes of Japanese Wilms' and other harvested within 96 h from the start of culture. Peripheral lymphocytes were cultured for 72 h with phytohemagglutinin, to determine the Received 5/20/91; accepted 8/19/91. constitutional karyotype. Ethidium bromide was used for 2 h before The costs of publication of this article were defrayed in part by the payment the harvest, to elongate chromosomes in the lymphocytes. Chromo of page charges. This article must therefore be hereby marked advertisement in somes were analyzed by Q- and/or G-banding techniques. Karyotypes accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1This work was supported in part by Grants-in-Aid from the Ministry of were described according to the International System for Human Cy Health and Welfare and the Ministry of Education, Science, and Culture of Japan. togenetic Nomenclature (27). We defined abnormal clones as two or 2To whom requests for reprints should be addressed, at Department of Laboratory Medicine, Saitama Cancer Center, Ina, Saitama, 362, Japan. 3The abbreviation used is: AWTA, aniridia-Wilms' tumor association. 5937

Downloaded from cancerres.aacrjournals.org on September 23, 2021. © 1991 American Association for Cancer Research. CHROMOSOMES IN WILMS' TUMOR more metaphase cells with identical structural and/or numerical chro mosome abnormalities. When we found only normal metaphase cells in the cultured tissue and cells spreading from the minced tumor pieces appeared to be fibroblasts, by inverted microscope analysis, the exami nation was considered to have failed to detect mitotic malignant cells .. and, hence, to be inadequate. We considered that normal diploid cells represented the karyotype of malignant cells in the tumor when all the five or more cells we karyotyped were diploid and when the cultured tumor cells did not appear to be fibroblasts. Even with the use of these criteria, the possibility that normal diploid karyotype may have be longed to normal reactive cells in the tumors still exists.

RESULTS HistolÃ³gica! Studies. Thirty-three tumors whose chromo somes were successfully examined were histologically classified by one of the authors (J. H.). Twenty-four were classified as typical Wilms' tumor and one as fetal rhabdomyomatous nephroblastoma. Two tumors were classified as cystic partially dif 558*'Ã®8 ferentiated nephroblastoma (Fig. 1); one (No. 384) of them included an area showing blastema! component. None of the Fig. 2. Patient 608. Clear cell sarcoma of the kidney, showing a diffuse 27 tumors showed focal or diffuse anaplastic lesions. Four proliferation of water clear cells with round normochromatic nuclei (24) (H & E, tumors were classified as clear cell sarcoma of the kidney; one x 200). (No. 608) of them showed myxoid mesenchymal tissue with arborizing vasculature (Fig. 2). Two tumors were diagnosed as congenital mesoblastic nephroma (Fig. 3). Chromosome Studies. Of the 33 childhood renal tumors, 31 were obtained from the primary sites at the time of diagnosis and two from the metastatic sites at relapse. Chromosomes were analyzed in resected tumors from 30 patients, in a xenograft from one (No. 27), in a resected tumor and its xenograft from one (No. 12), and in a cell line from one (No. 22). The examination was unsuccessful in the remaining seven tumors; no mitotic cells were found in four, and only normal diploid cells in three whose cultured cells appeared to be fibroblasts. Chromosomes and Histology in Wilms' Tumor and Other Childhood Renal Tumors. Of 24 typical Wilms' tumors, four had only normal diploid and/or tetraploid karyotypes, and the other 20 had clonal chromosome abnormalities. There were 12 hyperdiploid tumors, seven pseudodiploid tumors, and one hypodiploid tumor. Modal chromosome numbers in the hyper-

Fig. 3. Patient 544. Congenital mesoblastic nephroma, showing a varied cellular growth of spindle cells. The tumor is considered to be a benign tumor of infancy (26) (H & E, x 200).

diploid tumors ranged between 47 and 65, and trisomies were found in chromosomes 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 17, 18, 19, 20, and 22. The trisomies 2, 6, 7, 8, 10, 12, 13, 17, 18, and 20 were each seen in four of more tumors (Table 1). Three hyperdiploid tumors had only numerical abnormalities, and the other nine had numerical as well as structural abnormalities. Partial or total Iq polysomy, i.e., trisomy, tetrasomy, or pen- tasomy, was seen in three hyperdiploid and four pseudodiploid tumors. Of seven pseudodiploid tumors, two had monosomy 21. An 11pi3 deletion was found in two hyperdiploid tumors and two pseudodiploid tumors; two of the four were associated with aniridia. Other partial chromosome deletions included 7pâ€”in two tumors and Ipâ€”,2pâ€”,llqâ€”, 14qâ€”,and 17pâ€”in one each. One tumor not associated with aniridia had an Fig. l. Patient 74. Cystic partially differentiated nephroblastoma. A cystic inversion with breaks in 1Ipl3 and 1Iql3.5 (Fig. 4). encapsulated tumor with septal wall composed of flattened epithelial lining, Two cystic partially differentiated nephroblastomas had hy underlying cellular strema, rhabdomyomatous cells, and other foci resembling typical Wilms' tumor. The tumor occurs before 2 years of age (23) (H & E, x perdiploid karyotypes with 50 chromosomes, and extra chro 100). mosomes found in the two tumors were similar to those found 5938

Table 1 Clinical, histological, and karyotypic findings on 31 H'Urns' tumors and two other childhood renal tumors

Age Survival Histology of renal Tumor tumor" Patient (years) Sex Stage (months) Karyotype 2 4 M II 5 Typical Wilms'tumor (F) X 46,XY,-21.+i(lq) 22* 2 F l 90+ Typical Wilms' tumor (F) C 47,XX.+20.del(ll)(pl3pl4) 89 7.2 M I 61+ Typical Wilms'tumor (F) P 48.XY.+10.+12/50.X Y.+2,+8,+10,+12 148 14 M IV 29 Typical Wilms'tumor (F) P 46.XY.il 17q)/47.X Y,+12(SCA') 165' I F III 56+ Typical Wilms'tumor (F) P 46.XX.del(ll)(pl2pl3) 207 2 F III 49+ Typical Wilms'tumor (F) P 54,X,-X,+2,+6,+7,+12,+13.+17,+18. +r,+mar 275 1 F I 39+ Typical Wilms' tumor (F) P 48.XX.+3.+6 276 10 F 1 39+ Typical Wilms'tumor (F) P (p32),+3mar 312 4 F III 37+ Typical WJims'tumor (F) P 46.XX,del(11 )(pl 3p 14).dup( 1)(q21 -q44)/ 46.XX,-2,del( 11)(pl 3p 14).+der(2)t( 1: 2)(qll;p25) 325 IMI 36+ Typical Wilms" tumor (F) P 47,XY.+8,del(14)(q22) 392 13 F I 28 Typical Wilms'tumor (F) M 54,X,-X,-4.+6,+7,+9,-12.+13,+20,del ( 11)(p 13p 14).+i( 1q).+dcr(4)t(4;?)(p 12: ?),+4mar 519 3 M III 20+ Typical Wilms'tumor (F) P 46,XY,-19,-21.+i(lq).+dcr(19)t(19;?)(q 13;?) 521 2 F III 20+ Typical Wilms" tumor (F) P 52,XX,+2?,+5?,+12.+C.+ 14?.+ 18 528 4 F II 20+ Typical Wilms" tumor (F) P 56,XX,+5.+7.+7.+9.+10,+12,+13.+18. + 19.+22 539 l M III 18+ Typical Wilms'tumor (F) P 46.XY/92.XXYY 571 2 F II 17+ Typical Wilms'tumor (F) P 47.XX.+6 575 3 M II 15+ Typical Wilms'tumor (F) P 46.XY 619 2 M III 11+ Typical Wilms'tumor (F) P 5I.XY.+6.+8.+20.+der(7)t(7;?)(pl3;?),+ der(7)t(7;?)(pl3;?) 637 6 M IV 11+ Typical Wilms'tumor (F) P 46.XY/92.XXYY 640 3 M III 11+ Typical Wilms'tumor (F) P 46,XY.inv(ll)(pI3ql3.5) 667 3 M III 9+ Typical Wilms' tumor (F) P 46.XY.dup(l)(q21q32) 672 5 M II 8+ Typical Wilms' tumor (F) P 65,XXY.+2,+4,+6,+6.+7.+7.+8.+ 10.+ 12,+12,+13,+17,+17,+18.+20.+20. -22,+der( 14)t( 1;14)(q 12;p 13).+der( 15 )t( 1;15)(q 12;p 13),+der( 16)t( 1;16)(q 12: ql2) (F)TypicalWilms' tumor 74977174384299*1225759360847554412Va15232"/ii'/iiVaMFMMFMMMFMMIIIIIIIIIIIIIIVII4+2+76+31 (F)CysticW'ilms' tumor 13.+ 10,-ll,+ 12.+ 3).+der/17,+ 18,+der(7)t( 1;7)(q2 1;p 1 â€¢¿*Ã¬\IM1 1 \tf 1 1Â«'Ã•Wfil1 )50,X In 11,. M<|- 1, . differentiatednephroblastomapartially 750,X,-Y,+6,+Y.+7.+ 12,+ 13,+ 18/5 1,same.+ 1 (F)Cystic +37+582415+1024+19+Typicaldifferentiatednephroblastomapartially ;?),+der(?)t( 12,+ 13,+der(?)t( 1;?)(q2 1 (F)Fetal ;?)46.XX.t(10;ll)(pl3;pl3)46.XY46.XY46.XY46,XX,t(2;22)(q21;qll)47,X,-Y,+1;?)(q2 1 rhabdomyomatousnephroblastoma (F)Clear (U)Clearcell sarcoma XMPPPP92.XXYY56,XX,+2,+6,+8.+9.+ (U)Clearcell sarcoma (U)Clearcell sarcoma (U)Congenitalcell sarcoma ne-phromaCongenitalmesoblastic 3;q22),+dcr(11,- 17,t( 12; 15)(p 1 847,XY,+Yq 17q),+mar/48.same,+ 1 ne-phromaPPPPPP.mesoblastic 11/48.XY,+ 11,+ 11

" F. favorable histology; U, unfavorable histology. * C, cell line; P, primary tumor; M, metastatic lesion; X, xenograft. ' One cell line and two xenografts were established from untreated primary tumors. The primary tumors were studied before treatment, and the metastatic lesions were studied after treatment. ' AWTA. ' SCA, single-cell abnormality.

in the typical Wilms' tumors with hyperdiploidy (Table 1). DISCUSSION The only fetal rhabdomyomatous nephroblastoma had Chromosome Abnormalities in Wilms' Tumor. In the study of t(10;l I)(pl3;13) without other changes; this translocation was Japanese childhood renal tumors, we found that hyperdiploidy also seen in the constitutional cells of the patient (No. 299) with nonrandom trisomies was the most common cytogenetic (Fig. 5) who had aniridia. pattern in Wilms' tumor. On the basis of karyotypes summa Of four clear cell sarcomas of the kidney, three had only- rized from 133 Wilms' tumors reported by us and other inves normal diploid karyotype; a xenograft established from one of tigators (14-19), the distribution of the extra chromosomes are the three also showed normal karyotype, and the other had a shown in Fig. 7. Trisomy 12 was the most common and was 2;22 translocation as a sole chromosome abnormality (Fig. 6). found in 36 tumors (27%), followed by trisomies of 6, 7, 8, 9, Two congenital mesoblastic nephromas had hyperdiploid 10, 13, 18, or 20; each was seen in 13 or more tumors. A partial karyotypes with one or two extra chromosomes 11. Trisomy 11 or total Iq polysomy resulting from duplications, derivative was never seen in any of typical Wilms' tumors or cystic chromosomes, or isochromosomes was seen in 28 tumors partially differentiated nephroblastomas in the present series. (21%). High incidences of trisomies of 6, 7, 8, 9, 10, 12, 13, 5939

Downloaded from cancerres.aacrjournals.org on September 23, 2021. © 1991 American Association for Cancer Research. CHROMOSOMES IN WILMS' TUMOR 18, and 20 and Iq polysomy in Wilms' tumor indicate that genes, such as a cell growth factor or its receptor gene, may be present on these chromosomes or chromosome arms. We illustrated the deleted chromosomes or chromosome segments and the breakpoints of reciprocal translocations or inversions in the 133 Wilms' tumors in Fig. 8 (14-19). Dele l tions including 11pi3 and reciprocal translocations or an in version with a break at 11pi3 were found in 21 and three tumors, respectively. Deletions including 1Ipl5 and reciprocal translocations with a break in llplS were found in three and two tumors, respectively. Thus, chromosome abnormalities in volving 11pi3 or 11pi5 were recurrently found in Wilms' tumor, although the incidence of the 1Ipl5 abnormalities was much smaller than that of the 11pi3 abnormalities. These i findings are consistent with the data on allelic loss limited to Ilpl3or 11p15in some Wilms' tumor, shown by the restriction fragment length polymorphism study (9, 10). Other recurrent 2 2 chromosome deletions included chromosome Ip, 7p, 1Iq, 12q, Fig. 6. Partial karyotypes of two tumor cells from patient 608. Arrows, 16q, 17p, 21, and 22. Allelic loss of 1p, 16q, 17p, or 22 has translocation breakpoints in 2q21 and 22ql 1. been reported in various cancers (28, 29). Correlation of Karyotypes with Histology. Of three tumors developed in AWTA patients, two with the 1Ipl 3 deletion were

35 -I

30-

25- Ir Â«- 20-

Fig. 4. Partial karyotypes of two tumor cells from patient 640, showing a pericentric inversion of chromosome 11. Arrowheads, inversion breakpoints in -5. Ilpl3and llql3.S. r 10-

5 -

1 2 34 56 7 8 9 10 1112 13 14 15 16 17 18 19 20 21 22 X Y ?r u- Fig. 7. Diagram of chromosomal gains seen in 133 Wilms' tumors. Number of patients is on the vertical axis, and chromosome number is on the horizontal

classified as typical Wilms' tumor and one with 10 11 t(10;ll)(pl3;13) as fetal rhabdomyomatous nephroblastoma. Fig. 5. Partial karyotypes of two lymphocytes from patient 299. Arrowheads, Two of the three tumors had an 11 pi3 abnormality without translocationbreakpointsinI0pi3 and iipi3. other changes, and the other had trisomy 20 as an additional 5940

Fig. 8. Diagram of chromosome or chro mosome segment deletions seen in 133 Wilms' tumors. Chromosomes with deletions found in four or more tumors are shown. The chromo some regions corresponding to the vertical 11 lines were missing. Closed circles, transloca tion and inversion breakpoints.

16 17 22

change. Tumor karyotypes were reported in four other AWTA precise chromosomal and pathological studies, is essential to patients in the literature (16, 18, 19). Three of the four tumors elucidate whether typical Wilms' tumor and clear cell sarcoma had the 1Ipl3 deletion as a single abnormality, and the other of the kidney have different pathogenesis and should be classi had the 1Ipl3 deletion and trisomy 20. Thus, the tumor kary fied as different entities (24, 25). otypes found in the seven AWTA patients were rather simple, Congenital mesoblastic nephroma is considered to be a be and none had Iq polysomy or two or more extra chromosomes. nign tumor developing in infants of <6 months of age (26). We These findings suggest that only small DNA fragment deletions found trisomy or tetrasomy 11, with or without other changes, or point mutations in renal cells, which may not be detected by in two of two such nephromas. Although trisomies of chromo light microscopy, may be enough for the tumor development in some 12 and some other chromosomes were quite common in AWTA patients who already have a large DNA fragment dele typical Wilms' tumor, trisomy 11 was seen in only four (3%) of tion in 11pi 3 in their constitutional cells. the 133 Wilms' tumors (Fig. 7), and none in our series. Thus, Two tumors classified as cystic partially differentiated neph- trisomy 11 may be correlated with congenital mesoblastic ne roblastoma showed hyperdiploid karyotypes with 50 chromo phroma, and certain genes on chromosome 11 may play a role somes, including No. 12 trisomy. The hyperdiploid karyotype in the pathogenesis of this histolÃ³gica! type of tumor. with No. 12 trisomy was also reported in a tumor showing the None of the tumors in our series showed focal or diffuse same histology (30) and was commonly seen in typical Wilms' anaplastic lesions. Karyotypes from only seven anaplastic tumor. The karyotypic similarities may suggest a common Wilms' tumors were reported in the literature (15, 18, 19). Four genetic mechanism shared by both histolÃ³gica! types of tumors. of them had hypodiploidy or near-triploidy, with complex chro Karyotypes have been reported in 12 sarcomatous Wilms' mosome abnormalities, and the others had rather simple tumors, mostly specified as clear cell sarcoma of the kidney; changes. four were included in this series and eight in the literature (15, Karyotypic Patterns of Wilms1 Tumor between Japanese Pa 17-19, 31). Five tumors had only normal karyotype, and two tients and American and British Patients. Since the incidence of xenografts established from two of the five also showed normal Wilms' tumor in East Asian children was only one half to one karyotype. These findings imply that some sarcomatous Wilms' third of that in Caucasian children (13), we compared the tumors may not show microscopically detectable chromosome chromosome and histolÃ³gica! patterns between the Japanese changes. Of the seven tumors with chromosome abnormalities, tumors and the American and British tumors, to clarify whether one had hypodiploidy, three had pseudodiploidy, and three had the difference in the incidence reflects differences in karyotype hyperdiploidy with 47 chromosomes. None had a hyperdiploid or histology (14-19). Two Japanese series (Ref. 19 and our karyotype with 48 or more chromosomes, which was frequently data) and five American and British series (14-18) included 52 found in typical Wilms' tumor. Three had del(ll)(pl3pl4) or and 82 tumors, respectively. There was no significant difference lip- chromosome and two had reciprocal translocations, in the distribution of the tumor cell ploidies or in the presence which were rare in typical Wilms' tumor. The diverse kary of the tumors with the Ilpl3 abnormalities between the two otypes may reflect heterogeneous subgroups among sarcoma populations. There was also no significant difference in the tous Wilms' tumors. Accumulation of data on the tumors, with percentage of clear cell sarcoma or anaplastic Wilms' tumor 5941

Downloaded from cancerres.aacrjournals.org on September 23, 2021. © 1991 American Association for Cancer Research. CHROMOSOMES IN WILMS' TUMOR between the two populations. Thus, the higher incidence of G. A. P. Homozygous deletion in Wilms tumours of a zinc-finger gene VVilms' tumor in Caucasian children was not related to the identified by chromosome jumping. Nature (Lond.), 343: 774-778, 1990. 9. Reeve, A. E., Sin, S. A., Raizis, A. M., and Feinberg, A. P. Loss of allelic predominance of Wilms' tumors with specific chromosome heterozygosity at a second locus on chromosome 11 in sporadic Wilms' tumor cells. Mol. Cell. Biol., 9: 1799-1803, 1989. patterns or certain histolÃ³gica! subtypes. 10. Koufos, A., Grundy, P., Morgan, K., Aleck, K. A., Hadro, T., Lampkin, B. In conclusion, chromosome abnormalities we reported here C., Kalbakji. A., and Cavenee, W. K. Familial Wiedemann-Beckwith syn drome and a second Wilms tumor locus both map to 1IplS.S. Am. J. Hum. were recurrent and were correlated with the histolÃ³gica! types Genet., â€¢¿*Â¥:711-719,1989. of childhood renal tumors. The abnormalities included not only 11. Grundy, P., Koufos, A., Morgan, K., Li, F. P., Meadows, A. T., and Cavenee, the already well known 11pi3 deletion but also 11pi5 abnor W. K. Familial predisposition to Wilms' tumour does not map to the short arm of chromosome 11. Nature (Lond.), 336: 374-378, 1988. malities, nonrandom trisomies, and certain chromosome or 12. Huff, V., Compton, D. A., Chao, L. Y., Strong, L. C, Geiser, C. F., and chromosome segment deletions. These abnormalities likely re Saunders, G. F. Lack of linkage of familial Wilms' tumour to chromosomal flect critical genetic changes which contribute to development band 1Ipl3. Nature (Lond.), 336: 377-378, 1988. 13. Parkin, D. M., Stiller, C. A., Draper, G. J., and Bieber, C. A. The interna and progression of these tumors. tional incidence of childhood cancer. Int. J. Cancer, 42: 511-520, 1988. 14. Kondo, K., Chilcote, R. R., Maurer, H. S., and Rowley, J. D. Chromosome abnormalities in tumor cells from patients with sporadic Wilms' tumor. ACKNOWLEDGMENTS Cancer Res., 44: 5376-5381, 1984. 15. Douglass, E. C., Wilimas, J. A., Green, A. A., and Look, T. Abnormalities of chromosomes 1 and 11 in Wilms' tumor. Cancer Genet. Cytogenet., 14: We are grateful to K. Kon for expert technical assistance and N. 331-338, 1985. Kobayashi and F. Shinonaga for secretarial assistance. We thank Dr. 16. Dao, D. D., Schroeder, W. T., Chao, L-Y., Kikuchi, H., Strong, L. C., T. Oka, Asahikawa Medical College (Asahikawa, Hokkaido); Dr. Y. Riccardi, V. M., Pathak, S., Nichols, W. W., Lewis, W. H., and Saunders, Hatae, National Sapporo Hospital (Sapporo, Hokkaido); Dr. T. Hir- G. F. Genetic mechanisms of tumor-specific loss of 11p DNA sequences in ama, Hokkaido Children's Medical Center (Otaru, Hokkaido); Dr. A. Wilms tumor. Am. J. Hum. Genet., 41: 202-217, 1987. 17. Sous, V., Pritchard, J., and Cowell, J. K. Cytogenetic changes in Wilms' Kikuta, Fukushima Medical College (Fukushima, Fukushima); Dr. Y. tumors. Cancer Genet. Cytogenet., 34: 223-234, 1988. Yamashita, Niigata University (Niigata, Niigata); Dr. I. Sekine, Na 18. Wang-Wuu, S., Soukup, S., Bove, K., Gotwals, B., and Lampkin, B. Chro tional Defense Medical College (Tokorozawa, Saitama); Drs. Y. Tsu- mosome analysis of 31 Wilms' tumors. Cancer Res., 50: 2768-2793, 1990. nematsu and Y. Tsuchida, National Children's Hospital (Setagaya-ku, 19. Inaba, T., Hayashi, Y., Hanada, R., and Yamamoto, K. Chromosome findings in 23 cases with Wilms' tumor (nephroblastoma). J. Jpn. Pediatr. Soc., 94: Tokyo); Dr. K. Hashizume, Tokyo University (Bunkyo-ku, Tokyo); Dr. 845-851, 1990. K. Nishihira, Kanagawa Children's Medical Center (Yokohama, Kan 20. D'Angio, G. J., Breslow, N., Beckwith, B., Bishop, H., Farewell, V., Good agawa); Dr. H. 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Downloaded from cancerres.aacrjournals.org on September 23, 2021. © 1991 American Association for Cancer Research. Correlation of Chromosome Abnormalities with Histological and Clinical Features in Wilms' and Other Childhood Renal Tumors

Yasuhiko Kaneko, Chieko Homma, Nobuo Maseki, et al.

Cancer Res 1991;51:5937-5942.

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