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British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Dec;74(12):1975–1978. doi: 10.1038/bjc.1996.662

MYCL genotypes and loss of heterozygosity in non-small-cell lung cancer.

K M Fong 1, Y Kida 1, P V Zimmerman 1, P J Smith 1
PMCID: PMC2074830  PMID: 8980399

Abstract

Some studies have suggested that the S allele of the MYCL oncogene, which results from an intragenic EcoRI restriction fragment length polymorphism (RFLP), may be associated with cancer susceptibility. In addition, this allele has also been linked to metastases and adverse survival in certain cancers, although studies of lung cancer patients from different populations have yielded controversial results. We studied 108 cases of surgical resected non-small-cell lung cancer (NSCLC) and found no evidence that MYCL genotypes were associated with tumour progression or a worse prognosis. However, the presence of loss of heterozygosity (LOH) at this chromosome 1p32 locus correlated significantly with regional lymph node involvement, as well as advanced TNM stage. These data indicate the existence of a chromosome 1p candidate tumour-suppressor gene(s), possibly in linkage disequilibrium with the EcoRI RFLP in specific populations, which appears to play a role in determining tumour progression in NSCLC. Refined mapping of the critical region of loss should help attempts to identify and clone the candidate gene.

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Selected References

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  1. Bergh J. C. Gene amplification in human lung cancer. The myc family genes and other proto-oncogenes and growth factor genes. Am Rev Respir Dis. 1990 Dec;142(6 Pt 2):S20–S26. doi: 10.1164/ajrccm/142.6_Pt_2.S20. [DOI] [PubMed] [Google Scholar]
  2. Bieche I., Champeme M. H., Merlo G., Larsen C. J., Callahan R., Lidereau R. Loss of heterozygosity of the L-myc oncogene in human breast tumors. Hum Genet. 1990 Jun;85(1):101–105. doi: 10.1007/BF00276332. [DOI] [PubMed] [Google Scholar]
  3. Borg A., Zhang Q. X., Olsson H., Wenngren E. Chromosome 1 alterations in breast cancer: allelic loss on 1p and 1q is related to lymphogenic metastases and poor prognosis. Genes Chromosomes Cancer. 1992 Nov;5(4):311–320. doi: 10.1002/gcc.2870050406. [DOI] [PubMed] [Google Scholar]
  4. Caron H., van Sluis P., de Kraker J., Bökkerink J., Egeler M., Laureys G., Slater R., Westerveld A., Voûte P. A., Versteeg R. Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma. N Engl J Med. 1996 Jan 25;334(4):225–230. doi: 10.1056/NEJM199601253340404. [DOI] [PubMed] [Google Scholar]
  5. Chenevix-Trench G., Southall M., Kidson C. Restriction fragment length polymorphisms of L-myc and myb in human leukaemia and lymphoma in relation to age-selected controls. Br J Cancer. 1989 Dec;60(6):872–874. doi: 10.1038/bjc.1989.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crossen P. E., Morrison M. J., Colls B. M. Increased frequency of the S allele of the L-myc oncogene in non-Hodgkin's lymphoma. Br J Cancer. 1994 Apr;69(4):759–761. doi: 10.1038/bjc.1994.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dracopoli N. C., Harnett P., Bale S. J., Stanger B. Z., Tucker M. A., Housman D. E., Kefford R. F. Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4614–4618. doi: 10.1073/pnas.86.12.4614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Enomoto H., Ozaki T., Takahashi E., Nomura N., Tabata S., Takahashi H., Ohnuma N., Tanabe M., Iwai J., Yoshida H. Identification of human DAN gene, mapping to the putative neuroblastoma tumor suppressor locus. Oncogene. 1994 Oct;9(10):2785–2791. [PubMed] [Google Scholar]
  9. Fong K. M., Zimmerman P. V., Smith P. J. Microsatellite instability and other molecular abnormalities in non-small cell lung cancer. Cancer Res. 1995 Jan 1;55(1):28–30. [PubMed] [Google Scholar]
  10. Grundy P. E., Telzerow P. E., Breslow N., Moksness J., Huff V., Paterson M. C. Loss of heterozygosity for chromosomes 16q and 1p in Wilms' tumors predicts an adverse outcome. Cancer Res. 1994 May 1;54(9):2331–2333. [PubMed] [Google Scholar]
  11. Guan K. L., Jenkins C. W., Li Y., Nichols M. A., Wu X., O'Keefe C. L., Matera A. G., Xiong Y. Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. Genes Dev. 1994 Dec 15;8(24):2939–2952. doi: 10.1101/gad.8.24.2939. [DOI] [PubMed] [Google Scholar]
  12. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  13. Hoggard N., Brintnell B., Howell A., Weissenbach J., Varley J. Allelic imbalance on chromosome 1 in human breast cancer. II. Microsatellite repeat analysis. Genes Chromosomes Cancer. 1995 Jan;12(1):24–31. doi: 10.1002/gcc.2870120105. [DOI] [PubMed] [Google Scholar]
  14. Ikeda I., Ishizaka Y., Ochiai M., Sakai R., Itabashi M., Onda M., Sugimura T., Nagao M. No correlation between L-myc restriction fragment length polymorphism and malignancy of human colorectal cancers. Jpn J Cancer Res. 1988 Jun;79(6):674–676. doi: 10.1111/j.1349-7006.1988.tb02220.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ishizaki K., Kato M., Ikenaga M., Honda K., Ozawa K., Toguchida J. Correlation of L-myc genotypes to metastasis of gastric cancer and breast cancer. J Natl Cancer Inst. 1990 Feb 7;82(3):238–239. doi: 10.1093/jnci/82.3.238. [DOI] [PubMed] [Google Scholar]
  16. Kakehi Y., Yoshida O. Restriction fragment length polymorphism of the L-myc gene and susceptibility to metastasis in renal cancer patients. Int J Cancer. 1989 Mar 15;43(3):391–394. doi: 10.1002/ijc.2910430307. [DOI] [PubMed] [Google Scholar]
  17. Kato M., Toguchida J., Honda K., Sasaki M. S., Ikenaga M., Sugimoto M., Yamaguchi T., Kotoura Y., Yamamuro T., Ishizaki K. Elevated frequency of a specific allele of the L-myc gene in male patients with bone and soft-tissue sarcomas. Int J Cancer. 1990 Jan 15;45(1):47–49. doi: 10.1002/ijc.2910450110. [DOI] [PubMed] [Google Scholar]
  18. Kawashima K., Nomura S., Hirai H., Fukushi S., Karube T., Takeuchi K., Naruke T., Nishimura S. Correlation of L-myc RFLP with metastasis, prognosis and multiple cancer in lung-cancer patients. Int J Cancer. 1992 Feb 20;50(4):557–561. doi: 10.1002/ijc.2910500411. [DOI] [PubMed] [Google Scholar]
  19. Kawashima K., Shikama H., Imoto K., Izawa M., Naruke T., Okabayashi K., Nishimura S. Close correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human lung cancer to the lymph nodes and other organs. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2353–2356. doi: 10.1073/pnas.85.7.2353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kaye F., Battey J., Nau M., Brooks B., Seifter E., De Greve J., Birrer M., Sausville E., Minna J. Structure and expression of the human L-myc gene reveal a complex pattern of alternative mRNA processing. Mol Cell Biol. 1988 Jan;8(1):186–195. doi: 10.1128/mcb.8.1.186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lahti J. M., Valentine M., Xiang J., Jones B., Amann J., Grenet J., Richmond G., Look A. T., Kidd V. J. Alterations in the PITSLRE protein kinase gene complex on chromosome 1p36 in childhood neuroblastoma. Nat Genet. 1994 Jul;7(3):370–375. doi: 10.1038/ng0794-370. [DOI] [PubMed] [Google Scholar]
  22. Laurent-Puig P., Olschwang S., Delattre O., Remvikos Y., Asselain B., Melot T., Validire P., Muleris M., Girodet J., Salmon R. J. Survival and acquired genetic alterations in colorectal cancer. Gastroenterology. 1992 Apr;102(4 Pt 1):1136–1141. [PubMed] [Google Scholar]
  23. Leister I., Weith A., Brüderlein S., Cziepluch C., Kangwanpong D., Schlag P., Schwab M. Human colorectal cancer: high frequency of deletions at chromosome 1p35. Cancer Res. 1990 Nov 15;50(22):7232–7235. [PubMed] [Google Scholar]
  24. Mäkelä T. P., Hellsten E., Vesa J., Alitalo K., Peltonen L. An Alu variable polyA repeat polymorphism upstream of L-myc at 1p32. Hum Mol Genet. 1992 Jun;1(3):217–217. doi: 10.1093/hmg/1.3.217-a. [DOI] [PubMed] [Google Scholar]
  25. Nagai M. A., Yamamoto L., Salaorni S., Pacheco M. M., Brentani M. M., Barbosa E. M., Brentani R. R., Mazoyer S., Smith S. A., Ponder B. A. Detailed deletion mapping of chromosome segment 17q12-21 in sporadic breast tumours. Genes Chromosomes Cancer. 1994 Sep;11(1):58–62. doi: 10.1002/gcc.2870110109. [DOI] [PubMed] [Google Scholar]
  26. Nau M. M., Brooks B. J., Battey J., Sausville E., Gazdar A. F., Kirsch I. R., McBride O. W., Bertness V., Hollis G. F., Minna J. D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature. 1985 Nov 7;318(6041):69–73. doi: 10.1038/318069a0. [DOI] [PubMed] [Google Scholar]
  27. Saranath D., Panchal R. G., Nair R., Mehta A. R., Sanghavi V., Deo M. G. Restriction fragment length polymorphism of the L-myc gene in oral cancer patients. Br J Cancer. 1990 Apr;61(4):530–533. doi: 10.1038/bjc.1990.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sato S., Nakamura Y., Tsuchiya E. Difference of allelotype between squamous cell carcinoma and adenocarcinoma of the lung. Cancer Res. 1994 Nov 1;54(21):5652–5655. [PubMed] [Google Scholar]
  29. Shiraishi M., Noguchi M., Shimosato Y., Sekiya T. Amplification of protooncogenes in surgical specimens of human lung carcinomas. Cancer Res. 1989 Dec 1;49(23):6474–6479. [PubMed] [Google Scholar]
  30. Slebos R. J., Evers S. G., Wagenaar S. S., Rodenhuis S. Cellular protoonocogenes are infrequently amplified in untreated non-small cell lung cancer. Br J Cancer. 1989 Jan;59(1):76–80. doi: 10.1038/bjc.1989.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stoler A., Bouck N. Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transformation. Proc Natl Acad Sci U S A. 1985 Jan;82(2):570–574. doi: 10.1073/pnas.82.2.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tamai S., Sugimura H., Caporaso N. E., Resau J. H., Trump B. F., Weston A., Harris C. C. Restriction fragment length polymorphism analysis of the L-myc gene locus in a case-control study of lung cancer. Int J Cancer. 1990 Sep 15;46(3):411–415. doi: 10.1002/ijc.2910460314. [DOI] [PubMed] [Google Scholar]
  33. Taylor J. A., Bell D. A., Nagorney D. L-myc proto-oncogene alleles and susceptibility to hepatocellular carcinoma. Int J Cancer. 1993 Jul 30;54(6):927–930. doi: 10.1002/ijc.2910540610. [DOI] [PubMed] [Google Scholar]
  34. Tefre T., Børresen A. L., Aamdal S., Brøgger A. Studies of the L-myc DNA polymorphism and relation to metastasis in Norwegian lung cancer patients. Br J Cancer. 1990 Jun;61(6):809–812. doi: 10.1038/bjc.1990.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tsuchiya E., Nakamura Y., Weng S. Y., Nakagawa K., Tsuchiya S., Sugano H., Kitagawa T. Allelotype of non-small cell lung carcinoma--comparison between loss of heterozygosity in squamous cell carcinoma and adenocarcinoma. Cancer Res. 1992 May 1;52(9):2478–2481. [PubMed] [Google Scholar]
  36. Tsutsumi M., Yokota J., Kakizoe T., Koiso K., Sugimura T., Terada M. Loss of heterozygosity on chromosomes 1p and 11p in sporadic pheochromocytoma. J Natl Cancer Inst. 1989 Mar 1;81(5):367–370. doi: 10.1093/jnci/81.5.367. [DOI] [PubMed] [Google Scholar]
  37. Weiss J., Rubinfeld B., Polakis P. G., McCormick F., Cavenee W. K., Arden K. C. The RAP1GA1 locus for human Rap1-GTPase activating protein 1 maps to chromosome 1p36.1-->p35. Cytogenet Cell Genet. 1994;66(1):18–21. doi: 10.1159/000133655. [DOI] [PubMed] [Google Scholar]
  38. Weith A., Martinsson T., Cziepluch C., Brüderlein S., Amler L. C., Berthold F., Schwab M. Neuroblastoma consensus deletion maps to 1p36.1-2. Genes Chromosomes Cancer. 1989 Nov;1(2):159–166. doi: 10.1002/gcc.2870010209. [DOI] [PubMed] [Google Scholar]
  39. Weston A., Caporaso N. E., Perrin L. S., Sugimura H., Tamai S., Krontiris T. G., Trump B. F., Hoover R. N., Harris C. C. Relationship of H-ras-1, L-myc, and p53 polymorphisms with lung cancer risk and prognosis. Environ Health Perspect. 1992 Nov;98:61–67. doi: 10.1289/ehp.929861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Weston A., Ling-Cawley H. M., Caporaso N. E., Bowman E. D., Hoover R. N., Trump B. F., Harris C. C. Determination of the allelic frequencies of an L-myc and a p53 polymorphism in human lung cancer. Carcinogenesis. 1994 Apr;15(4):583–587. doi: 10.1093/carcin/15.4.583. [DOI] [PubMed] [Google Scholar]
  41. Yokota J., Wada M., Yoshida T., Noguchi M., Terasaki T., Shimosato Y., Sugimura T., Terada M. Heterogeneity of lung cancer cells with respect to the amplification and rearrangement of myc family oncogenes. Oncogene. 1988 Jun;2(6):607–611. [PubMed] [Google Scholar]
  42. Young J., Buttenshaw R., Butterworth L., Ward M., Searle J., Leggett B., Chenevix-Trench G. Association of the SS genotype of the L-myc gene and loss of 18q sequences with a worse clinical prognosis in colorectal cancers. Oncogene. 1994 Apr;9(4):1053–1056. [PubMed] [Google Scholar]

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