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Proto-oncogene allelic variations in human squamous cell carcinomas of the larynx

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Summary

Proto-oncogene restriction fragment length polymorphisms (RFLPs) were investigated in a group of 23 patients with squamous cell carcinomas of the larynx. The frequency of the rare 5 kb c-mos allele was significantly higher than that observed in control groups of patients with colorectal neoplasms or lymphoproliferative disorders. In addition, the 2 patients heterozygous at the c-mos locus (TC-8 and TC-10) were the only 2 of our series to develop multiple malignancies. Also, the 10 kb L-myc allele was remarkably more represented in patients with laryngeal carcinoma when compared to controls. These findings suggest that c-mos and L-myc RFLPs might be helpful in identifying those individuals who are at a higher risk of developing laryngeal carcinomas. Single allele amplification of L-myc, c-myb and c-mos proto-oncogenes, with no concomitant mRNA hyperexpression, were observed in 3 cases. The results obtained seem to rule out a direct pathogenetic role of these proto-oncogenes and suggest that the amplification of other closely linked genes, located on chromosomes 1, 6 and 8, respectively, may be causally associated with the development of these tumors. No allelic deletions at the c-myb locus were observed, whereas a loss of a c-Ha-ras-1 allele was demonstrated in one of the 11 heterozygous patients. Thus, the analysis of polymorphic proto-oncogenes in laryngeal carcinomas allowed us to identify a group of genetic abnormalities (chromosomes 1, 6 and 8 gene amplifications and c-Ha-ras-1 deletions) which may be involved in the development or progression of these tumors.

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References

  1. Ali IU, Lidereau R, Theillet C, Callahan R (1987) Reduction to homozygosity of genes on chromosome 11 in human breast neoplasia. Science 238:185–188

    Google Scholar 

  2. Armitage P, Berry G (1987) Statistical methods in medical research, 2nd edn. Blackwell, Oxford, p 115

    Google Scholar 

  3. Atkinson D, Fleming S, Weaver A (1982) Triple endoscopy: a valuable procedure in head and neck surgery. Am J Surg 144: 416–419

    Google Scholar 

  4. Bishop JM (1983) Cellular oncogenes and retroviruses. Annu Rev Biochem 52:301–354

    Google Scholar 

  5. Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 32:314–331

    CAS  PubMed  Google Scholar 

  6. Chenevix-Trench G, Southall M, Kidson C (1989) Restriction fragment length polymorphisms of L-myc and myb in human leukaemia and lymphoma in relation to age-selected controls. Br J Cancer 60:872–874

    Google Scholar 

  7. Chenevix-Trench G, Southall M, Kidson C (1989) The EcoRI RFLP c-mos in patients with non-Hodgkin's lymphoma and acute lymphoblastic leukaemia, compared to geriatric and non-geriatric controls. Int J Cancer 43: 1034–1036

    Google Scholar 

  8. Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299

    CAS  PubMed  Google Scholar 

  9. Cline MJ, Battifora H (1987) Abnormalities of protooncogenes in non-small cell lung cancer, correlations with tumor type and clinical characteristics. Cancer 60:2669–2674

    Google Scholar 

  10. Cohn A, Peppard S (1980) Multiple primary malignant tumors of the head and neck. Am J Otol 1: 411–417

    Google Scholar 

  11. Corell B, Zoll B (1988) Evidence against a tumour-specific EcoRI RFLP of the c-mos locus. FEBS Lett 230:81–84

    Google Scholar 

  12. Diedrich U, Eckermann O, Schmidtke J (1988) Rare Ha-ras and c-mos alleles in patients with intracranial tumors. Neurology 38:587–589

    Google Scholar 

  13. Dolcetti R, De Re V, Viel A, Pistello M, Tavian M, Boiocchi M (1988) Nuclear oncogene amplification or rearrangement is not involved in human colorectal malignancies. Eur J Cancer Clin Oncol 24:1321–1328

    Google Scholar 

  14. Dozier C, Walbaum S, Leprince D, Stehelin D (1986) EcoRI RFLP linked to the human myb gene. Nucleic Acids Res 14: 1928

    Google Scholar 

  15. Duesberg PH (1985) Activated proto-oncogenes: sufficient or necessary for cancer? Science 228:669–677

    Google Scholar 

  16. 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

    Google Scholar 

  17. Fitzpatrick PJ, Tepperman BS, DeBoer G (1984) Multiple primary squamous cell carcinomas in the upper digestive tract. Int J Radiat Oncol Biol Phys 10:2273–2279

    Google Scholar 

  18. Gluckman JL, Crissman JD (1983) Survival rates in 548 patients with multiple neoplasms of the upper aerodigestive tract. Laryngoscope 93:71–74

    Google Scholar 

  19. Heighway J, Thatcher N, Cerny T, Hasleton PS (1986) Genetic predisposition to human lung cancer. Br J Cancer 53:453–457

    Google Scholar 

  20. Heim S, Mitelman F (1987) Cancer cytogenetics. Liss, New York

    Google Scholar 

  21. Hollstein M, Montesano R, Yamasaki H (1986) Presence of an EcoRI RFLP of the c-mos locus in normal and tumor tissue of esophageal cancer patients. Nucleic Acids Res 14:86–95

    Google Scholar 

  22. Hordijk GJ, DeJong JMA (1983) Synchronous and metachronous tumours in patients with head and neck cancer. J Laryngol Otol 97:619–621

    Google Scholar 

  23. Howell RE, Wong FSH, Fenwick RG (1989) Loss of Harvey ras heterozygosity in oral squamous carcinoma. J Oral Pathol Med 18:79–83

    Google Scholar 

  24. Ikeda I, Ishizaka Y, Ochiai M, Sakai R, Itabashi M, OndaM, Sugimura T, Nagao M (1988) No correlation between L-myc restriction fragment length polymorphism and malignancy of human colorectal cancers. Gann 79:674–676

    Google Scholar 

  25. Jin YS, Mandahl N, Heim S, Biorklund A, Wennerberg J, Mitelman F (1988) Unique karyotypic abnormalities in a squamous cell carcinoma of the larynx. Cancer Genet Cytogenet 30:177–179

    Google Scholar 

  26. Kahehi Y, Yoshida O (1989) Restriction fragment length polymorphism of the L-myc gene and susceptibility to metastasis in renal cancer patients. Int J Cancer 43:391–394

    Google Scholar 

  27. Klein G (1987) The approaching era of the tumor suppressor genes. Science 238:1539–1545

    Google Scholar 

  28. Klein G, Klein E (1985) Evolution of tumors and the impact of molecular oncology. Nature 315:190–195

    Google Scholar 

  29. Knudson AG Jr (1985) Hereditary cancer, oncogenes and antioncogenes. Cancer Res 45: 1437–1443

    Google Scholar 

  30. 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

    Google Scholar 

  31. Krontiris T, DiMartino N, Colb M, Parkinson D (1985) Unique allelic restriction fragments of the Ha-ras locus in leucocyte and tumour DNAs of cancer patients. Nature 313:369–373

    Google Scholar 

  32. Kurosawa H, Yamada M, Nakagome Y (1987) Restriction fragment length polymorphisms of the human N-myc gene: relationship to gene amplification. Oncogene 2:85–90

    Google Scholar 

  33. Lee JH, Kavanagh JJ, Wharton JT, Wildrick DM, Blick M (1989) Allele loss at the c-H-ras-1 locus in human ovarian cancer. Cancer Res 49:1220–1222

    Google Scholar 

  34. Lidereau R, Mathieu-Mahul D, Theillet C, Renaud M, Mauchauffe M, Gest J, Larsen CJ (1985) Presence of an allelic EcoRI restriction fragment of c-mos locus in leucocyte and tumour cell DNAs of breast cancer patients. Proc Natl Acad Sci USA 82:7068–7070

    Google Scholar 

  35. Lidereau R, Escot C, Theillet C, Champeme MH, Brunet M, Gest J, Callahan R (1986) High frequency of rare alleles of the human c-Ha-ras-1 proto-oncogene in breast cancer patients. J Natl Cancer Inst 77:697–701

    Google Scholar 

  36. Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, New York

    Google Scholar 

  37. Masaki N, Hashimoto T, Ikeda H, Inoue T, Kozuka T (1987) Multiple primary malignancies in patients with head and neck cancer. Jpn J Clin Oncol 17:303–307

    Google Scholar 

  38. Meier R (1988) A universal and efficient protocol for the isolation of RNA from tissues and cultured cells. Nucleic Acids Res 16:2340

    Google Scholar 

  39. Mitelman F (1985) Catalog of chromosome aberrations in cancer. Liss, New York

    Google Scholar 

  40. Nan MM, Brooks BJ, Battey J, Sausville E, Gazdar AF, Kirsch IR, McBride OW, Bertness V, Hollis GF, Minna JD (1985) L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature 318:69–73

    Google Scholar 

  41. Pulciani S, Santos E, Lanuer AV, Long LK, Barbacid D (1982) Transforming genes in human tumors. J Cell Biochem 20:51–61

    Google Scholar 

  42. Revoltella RP, Park M, Fruscalzo A (1985) Identification in several human myeloid leukemias or cell lines of a DNA rearrangement next to the c-mos 3′-end. FEBS Lett 189:97–101

    Google Scholar 

  43. Sandberg AA, Turc-Caret C (1987) The cytogenetics of solid tumors. Relation to diagnosis, classification and pathology. Cancer 59:387–395

    Google Scholar 

  44. Schottenfeld D, Gantt RC, Wynder EL (1974) The role of alcohol and tobacco in multiple primary cancers of the upper digestive system, larynx and lung: a retrospective study. Prev Med 3:277–293

    Google Scholar 

  45. Shapshay SM, Hong WK, Fried MP, Sismanis A, Vaughan CW, Strong MS (1980) Simultaneous carcinoma of the esophagus and upper aerodigestive tract. Otolaryngol Head Neck Surg 88:373–377

    Google Scholar 

  46. Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517

    CAS  PubMed  Google Scholar 

  47. Theillet C, Lidereau R, Escot C, Hutzell P, Brunet M, Gest J, Schlom J, Callahan R (1986) Loss of a c-Ha-ras-1 allele and aggressive human primary breast carcinomas. Cancer Res 46: 4776–4781

    Google Scholar 

  48. Watson R, Oskarsson M, Vande Woude GF (1982) Human DNA sequence homologous to the transforming gene (mos) of Moloney murine sarcoma virus. Proc Natl Acad Sci USA 79: 4078–4082

    Google Scholar 

  49. Weichert KA, Schmrick D (1979) Multiple malignancies in patients with primary carcinoma of the head and neck. Laryngoscope 89:988–991

    Google Scholar 

  50. Yokota J, Tsunetsugu-Yokota Y, Battifora H, LeFevre C, Cline MJ (1986) Alterations of myc, myb, and Ha-ras protooncogenes in cancers are frequent and show clinical correlation. Science 231:261–265

    Google Scholar 

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Authors and Affiliations

  1. Division of Experimental Oncology I, Centro di Riferimento Oncologico, Via Pedemontana Occidentale, 133081, Aviano, PN, Italy

    R. Dolcetti, R. Maestro, S. Rizzo & M. Boiocchi

  2. Department of Otorhinolaringology, University of Ferrara, Ferrara, Italy

    S. Pelucchi & A. Pastore

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  1. R. Dolcetti
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  2. S. Pelucchi
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  5. A. Pastore
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  6. M. Boiocchi
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Dolcetti, R., Pelucchi, S., Maestro, R. et al. Proto-oncogene allelic variations in human squamous cell carcinomas of the larynx. Eur Arch Otorhinolaryngol 248, 279–285 (1991). https://doi.org/10.1007/BF00176755

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  • DOI: https://doi.org/10.1007/BF00176755

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