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Loss of heterozygosity in hypotriploid cell cultures from testicular tumours

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Summary

We have established cell lines with a hypotriploid chromosome number from four testicular tumours. Each line had at least one Y chromosome and most of the informative centromere and enzyme markers were heterozygous implying that the tumours originated from germ cells before the first meiotic division. The small metacentric marker chromosome (i12p), specific for testicular tumours, was present in all tumour cell lines and up to three copies were found in some lines. Rearrangements of chromosome 1 and 11 were each found in three out of four tumours. The rearrangements of chromosome 1 all resulted in duplication of 1q and deletion of short-arm material from the same chromosome giving loss of heterozygosity for enzyme markers on 1p. Loss of satellite material from chromosome 13 and the centromere region of chromosome 9 were found in single cases. This study shows that even where the chromosome number of tumour cells is near triploid, regions of the genome can be deleted. The chromosomes most frequently involved in rearrangements, 1, 11, and 12 all contain sites of ras oncogenes and it is suggested that loss of normal alleles could result in homozygosity for mutant oncogenes which may play a part in tumour progression.

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References

  • Atkin NB (1973) High chromosome numbers of seminomata and malignant teratomata of the testis: a review of data on 103 tumours. Br J Cancer 28:275–278

    CAS  PubMed  Google Scholar 

  • Atkin NB, Baker MC (1983) i(12p): Specific chromosomal marker in seminoma and malignant teratoma of the testis? Cancer Genet Cytogenet 10:199–204

    Article  CAS  PubMed  Google Scholar 

  • Atkin NB, Baker MC (1985) Chromosome analysis of three seminomas. Cancer Genet Cytogenet 17:315–323

    Article  CAS  PubMed  Google Scholar 

  • Aurias A, Rimbaut C, Buffe D, Zucker JM, Mazabraud A (1984) Translocation involving chromosome 22 in Ewing's sarcoma. A cytogenetic study of four fresh tumours. Cancer Genet Cytogenet 12:21–25

    Article  CAS  PubMed  Google Scholar 

  • Balaban G, Herlyn M, Guerry D, Bartolo R, Koprowski H, Clark WH, Nowell PC (1984) Cytogenetic of human malignant melanoma and premalignant lesions. Cancer Genet Cytogenet 11:429–439

    Article  CAS  PubMed  Google Scholar 

  • Benedict WF, Weisman BE, Mark C, Stanbridge EJ (1984) Tumorigenicity of human HT1080 fibrosarcoma x normal fibroblast hybrids: chromosome dosage dependency. Cancer Res 44: 3471–3479

    CAS  PubMed  Google Scholar 

  • Brito-Babapulle V, Atkin NB (1981) Breakpoints in chromosome 1: abnormalities of 218 human neoplasms. Cancer Genet Cytogenet 4:215–225

    Article  CAS  PubMed  Google Scholar 

  • Brodeur GM, Green AA, Hayes FA, Williams KJ, Williams DL, Tsiatis AA (1981) Cytogenetic features of human neuroblastomas and cell lines. Cancer Res 41:4678–4686

    CAS  PubMed  Google Scholar 

  • Carritt B, Parrington JM, Welch HM, Povey S (1982) Diverse origins of multiple ovarian teratomas in a single individual. Proc Natl Acad Sci USA 79:7400–7404

    CAS  PubMed  Google Scholar 

  • Cavenee WK, Dryja TP, Philips RA, Benedict WF, Godbout R, Gallie BL, Murphree AL, Strong LC, White RL (1983) Expression of recessive alleles by chromosomal mechanisms in retionoblastoma. Nature 305:779–784

    Article  CAS  PubMed  Google Scholar 

  • Davies JM (1981) Testicular cancer in England and Wales: some epidemiological aspects. Lancet I:928–931

    Google Scholar 

  • Delozier-Blanchet CD, Engel E, Walt H (1985) Isochromosome 12p in malignant testicular tumours. Cancer Genet Cytogenet 15:375–376

    Article  CAS  PubMed  Google Scholar 

  • Douglass EC, Green AA, Hayes FA, Etcubanas E, Horowitz M, Wilimas J (1985) Chromosome 1 abnormalities: a common feature of pediatric solid tumours. J Natl Cancer Inst 75:51–54

    CAS  PubMed  Google Scholar 

  • Dracopoli NC, Houghton AN, Old LJ (1985) Loss of polymorphic restriction fragments in malignant melanoma: implications for tumour heterogeneity. Proc Natl Acad Sci USA 82:1470–1474

    CAS  PubMed  Google Scholar 

  • Fearon ER, Feinberg AP, Hamilton SH, Vogelstein B (1985) Loss of genes on the short arm of chromosome 11 in bladder cancer. Nature 318:377–380

    Article  CAS  PubMed  Google Scholar 

  • Gibas Z, Prout GR, Pontes JE, Sandberg AA (1986) Chromosome changes in germ cell tumours of the testis. Cancer Genet Cytogenet 19:245–252

    CAS  PubMed  Google Scholar 

  • Gilbert F, Balaban G, Moorhead P, Bianchi D, Schlesinger H (1982) Abnormalities of chromosome 1p in human neuroblastoma tumours and cell lines. Cancer Genet Cytogenet 7:33–42

    Article  CAS  PubMed  Google Scholar 

  • Hall A, Marshall CJ, Spurr NK, Weiss RA (1983) Identification of a transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. Nature 303:396–400

    CAS  PubMed  Google Scholar 

  • Jones WG, Milford Ward A, Anderson CK (eds) (1985) Germ cell tumours II. Proceedings of the second Germ Cell Tumour Conference, Leeds. Pergamon Press, Oxford New York (Advances in biosciences, vol 55)

    Google Scholar 

  • Koufos A, Hansen MF, Copeland NG, Jenkins NA, Lampkin BC, Cavenee WK (1985) Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism. Nature 316:330–334

    Article  CAS  PubMed  Google Scholar 

  • Kovacs GY (1978) Anormalities of chromosome no. 1 in human solid malignant tumours. Int J Cancer 21:688–694

    CAS  PubMed  Google Scholar 

  • Martineau M (1969) Chromosomes in human testicular tumours. J Pathol 99:271–282

    Article  CAS  PubMed  Google Scholar 

  • Newlands ES, Reynolds KW (1983) Clinical management of malignant germ cell tumours. Cancer Surv 2:21–40

    Google Scholar 

  • Parrington JM, West LF, Povey S (1984) The origin of ovarian teratomas. J Med Genet 21:4–12

    CAS  PubMed  Google Scholar 

  • Povey S, Morton NE, Sherman SL (1985) Report of the Committee on the Genetic Constitution of Chromosomes 1 and 2. (8th International Workshop on Human Gene Mapping). Cytogenet Cell Genet 40:67–106

    CAS  PubMed  Google Scholar 

  • Reichman A, Martin P, Levin B (1984) Chromosomes in human large bowel tumours: a study of chromosome 1. Cancer Genet Cytogenet 12:295–301

    Google Scholar 

  • Rodgers CS, Hill SM, Hulten MA (1984) Cytogenetic analysis in human breast carcinoma. 1. Nine cases in the diploid range investigated using direct preparations. Cancer Genet Cytogenet 13:95–119

    Article  CAS  PubMed  Google Scholar 

  • Rowley JD (1977) Mapping of human chromosomal regions related to neoplasia: evidence from chromosomes 1 and 17. Proc Natl Acad Sci USA 74:5729–5733

    CAS  PubMed  Google Scholar 

  • Rowley JD (1983) Human oncogene locations and chromosome aberrations. Nature 301:290–291

    Article  CAS  PubMed  Google Scholar 

  • Santos E, Martin-Zanca D, Reddy EP, Pierotti MA, Della Porta G, Barbacid M (1984) Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient. Science 223:661–664

    CAS  PubMed  Google Scholar 

  • Shimizu K, Goldfarb M, Suard Y, Perucho M, Li Y, Kamata T, Feramisco J, Stavnezer E, Fogh J, Wigler MH (1983) Three human transforming genes are related to the viral ras oncogenes. Proc Natl Acad Sci USA 80:2112–2116

    CAS  PubMed  Google Scholar 

  • Shtivelman E, Lifshitz B, Gale RP, Canaani E (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 315:550–554

    Article  CAS  PubMed  Google Scholar 

  • Stoler A, Bouck N (1985) Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transformation. Proc Natl Acad Sci USA 82:570–574

    CAS  PubMed  Google Scholar 

  • Van der Sande JH, Lin CC, Deugau KV (1979) Clearly differentiated and stable chromosome bands produced by a spermine bis-acridine, a bifunctional intercalating analogue of quinacrine. Exp Cell Res 120:439–444

    PubMed  Google Scholar 

  • Wang N, Trend B, Bronson DL, Fraley EE (1980) Non random abnormalities in chromosome 1 in human testicular cancers. Cancer Res 40:796–802

    CAS  PubMed  Google Scholar 

  • Wang N, Perkins KL, Bronson DL, Fraley EE (1981) Cytogenetic evidence in premeiotic transformation of human testicular cancers. Cancer Res 41:2135–2140

    CAS  PubMed  Google Scholar 

  • Yunis JJ (1983) The chromosomal basis of human neoplasia. Science 221:227–236

    CAS  PubMed  Google Scholar 

Download references

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Parrington, J.M., West, L.F. & Povey, S. Loss of heterozygosity in hypotriploid cell cultures from testicular tumours. Hum Genet 77, 269–276 (1987). https://doi.org/10.1007/BF00284484

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