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Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival

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Summary

The distal half of chromosome 1p was analysed with 15 polymorphic microsatellite markers in 683 human solid tumours at different locations. Loss of heterozygosity (LOH) was observed at least at one site in 369 cases or 54% of the tumours. LOHs detected ranged from 30–64%, depending on tumour location. The major results regarding LOH at different tumour locations were as follows: stomach, 20/38 (53%); colon and rectum, 60/109 (55%); lung, 38/63 (60%); breast, 145/238 (61%); endometrium, 18/25 (72%); ovary, 17/31 (55%); testis, 11/30 (37%); kidney, 22/73 (30%); thyroid, 4/14 (29%); and sarcomas, 9/14 (64%). High percentages of LOH were seen in the 1p36.3, 1p36.1, 1p35–p34.3, 1p32 and 1p31 regions, suggesting the presence of tumour-suppressor genes. All these regions on chromosome 1p show high LOH in more than one tumour type. However, distinct patterns of LOH were detected at different tumour locations. There was a significant separation of survival curves, with and without LOH at chromosome 1p, in the breast cancer patients. Multivariate analysis showed that LOH at 1p in breast tumours is a better indicator for prognosis than the other variables tested in our model, including nodal metastasis.

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  1. Arlt, M. F., Herzog, T. J., Mutch, D. G., Gersell, D. J., Liu, H. & Goodfellow, P. J. (1996). Frequent deletions of chromosome 1p sequences of aggressive histologic subtype of endometrial cancer. Hum Mol Genet 5: 1017–1021.

    CAS  PubMed  Google Scholar 

  2. Bardi, G., Pandis, N., Fenger, C., Kronborg, O., Bomme, L. & Heim, S. (1993). Deletion of 1p36 as primary chromosomal aberration in intestinal tumorigenesis. Cancer Res, 53: 1895–1898.

    CAS  PubMed  Google Scholar 

  3. Bello, M. J., de Campos, J. M., Kusak, M. E., Vaquero, J., Sarasa, J. L., Pestana, A. & Rey, J. A. (1994). Allelic loss at 1p is associated with tumor progression of meningiomas. Genes Chromosom Cancer, 9: 296–298.

    CAS  PubMed  Google Scholar 

  4. Bieche, I., Champème, M. H. & Lidereau, R. (1994). A tumor suppressor gene on chromosome 1p32-pter controls the amplification of MYC family genes in breast cancer. Cancer Res 54: 4274–4276.

    CAS  PubMed  Google Scholar 

  5. Bodmer, J. L., Burns, K., Sneider, P., Hofmann, K., Steiner, V., Thome, M., Bornand, T., Hahne, M., Schroter, M., Becker, K., Wilson, A., French, L. E., Browning, J. L., MacDonald, H. R. & Tschopp, J. (1997). Tramp, a novel apotosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas(Apo-1/CD95). Immunity, 6: 79–88.

    CAS  Google Scholar 

  6. Buyse, I. M., Takahashi, E. I. & Huang, S. (1996). Physical mapping of retinoblastoma interacting zinc finger gene RIZ to D1S228 on chromosome 1p36. Genomics, 15: 119–121.

    Google Scholar 

  7. Caron, H., Peter, M., van Sluis, P., Speleman, F., de Kraker, J., Laureys, G., Michon, J., Brugieres, L., Voute, P. A., Westerveld, A., Slater, R., Delattre, O. & Versteeg, R. (1995). Evidence for two tumour suppressor loci on chromosomal bands 1p35–36 involved in neuroblastoma: one probably imprinted, another associated with N-myc amplification. Hum Mol Genet, 4: 535–539.

    CAS  PubMed  Google Scholar 

  8. Caron, H., van Sluis, P., de Kraker, J., Bokkerink, J., Egeler, M., Laureys, G., Slater, R., Westerveld, A., Voute, P. A. & Versteeg, R. (1996). Allelic loss of chromosome 1p as a predictor of unfavourable outcome in patients with neuroblastoma. N Engl J Med, 334: 225–230.

    CAS  PubMed  Google Scholar 

  9. Cavenee, W. K. & White, R. L. (1995). The genetic basis of cancer. An accumulation of genetic defects can apparently cause normal cells to become cancerous and cancerous cells to become increasingly dangerous. Sci Am (March) 72–79.

  10. Chase, P. B., Yang, J. M., Thompson, F. H., Halonen, M. & Regan, J. W. (1996). Regional mapping of the platelet-activating factor receptor gene (PTAFR) to 1p35–p34.3 by fluorescence in situ hybridisation. Cytogenet Cell Genet 72: 205–207.

    CAS  PubMed  Google Scholar 

  11. Chen, L. C., Kurisu, W., Ljung, B. M., Goldman, E. S., Moore, D. I. I. & Smith, H. S. (1992). Heterogeneity for allelic loss in human breast cancer. J Natl Cancer Inst 84: 506–510.

    CAS  PubMed  Google Scholar 

  12. Cox, D. R. (1972). Regression models and life-tables. J R Stat Soc (B) 34: 187–220.

    Google Scholar 

  13. Di Vinci, A., Infusini, E., Peveri, C., Risio, C., Rossini, F. P. & Giaretti, W. (1996). Deletions at chromosome 1p by fluorescence in situ hybridisation are an early event in human colorectal tumorigenesis. Gastroenterology 111: 102–107.

    CAS  PubMed  Google Scholar 

  14. Dracopoli, N. C., Harnett, P., Bale, S. J., Stanger, B. Z., Tucker, M. A., Housman, D. E. & Kefford, R. F. (1989). Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression. Proc Natl Acad Sci USA, 86: 4614–4618.

    CAS  PubMed  Google Scholar 

  15. Duncan, A. M. V., Anderson, L. L., Funk, C. D., Abramovitz, M. & Adam, M. (1995). Chromosomal localisation of the prostanoid receptor gene family. Genomics, 25: 740–742.

    CAS  PubMed  Google Scholar 

  16. Ezaki, T., Yanagisawa, A., Otha, K., Aiso, S., Watanabe, M., Hibi, T., Kato, Y., Nakajima, T., Ariyama, T., Inazawa, J., Nakamura, Y. & Horii, A. (1996). Deletions mapping on chromosome 1p in well-differentiated gastric cancer. Br J Cancer, 73: 424–428.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Haber, D. & Harlow, E. (1997). Tumor-suppressor genes: evolving definitions in the genomic age. Nat Genet 16: 320–322.

    CAS  PubMed  Google Scholar 

  18. Hey, Y., Hoggard, N., Brintnell, B., James, L., Jones, D., Mitchell, E., Weissenbach, J. & Varley, J. M. (1996). Identification and cloning in yeast artificial chromosomes of a region of elevated loss of heterozygosity on chromosome 1p31.1 in human breast cancer. Cytogenet Cell Genet, 72: 148

    Google Scholar 

  19. Johnson, D. W., Qumsiyeh, M. & Benkhalifa, M. (1995). Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFRBR1 and TGFBR3) to 9q33-q34 and 1p32–p33, respectively. Genomics, 28: 356–357.

    CAS  PubMed  Google Scholar 

  20. Kaghad, M., Bonnet, H., Yang, A., Creancier, L., Biscan, J. C., Valent, A., Minty, A., Chalon, P., Lelias, J. M., Dumont, X., Ferrara, P., McKeon, F. & Caput, D. (1997). Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell, 90: 809–819.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kaplan, E. L. & Meier, P. (1958). Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481.

    Google Scholar 

  22. Kemper, O., Derre, J., Cherif, D., Engelmann, H., Wallach, D. & Berger, R. (1991). The gene for the type II (p75) tumor necrosis factor receptor (TNF-RII) is localized on band 1p36.2–p36.3. Hum Genet, 87: 623–624.

    CAS  PubMed  Google Scholar 

  23. Kuroki, T., Fujiwara, Y., Tsuchiya, E., Nakamori, S., Imaoka, S., Kanematsu, T. & Nakamura, Y. (1995). Accumulation of genetic changes during development and progression of hepatocellular carcinoma: loss of heterozygosity of chromosome arm 1p occurs at an early stage of hepatocarcinogenesis. Genes Chromosom Cancer, 13: 163–167.

    CAS  PubMed  Google Scholar 

  24. Kwon, B. S., Tan, K. B., Ni, J., Lee, K. O., Kim, K. K., Kim, Y. J., Wang, S., Gentz, R., Yu, G. L., Harrop, J., Lyn, S. D., Silverman, C., Porter, T. G., Truneh, A. & Young, P. R. (1997). A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation. J Biol Chem 272: 14272–14276.

    CAS  PubMed  Google Scholar 

  25. Lahti, J. M., Valentine, M., Xiang, J., Jones, B., Amann, J., Grenet, J., Richmond, G., Look, A. T. & Kidd, V. J. (1994). Alteration in the PITSLRE protein kinase gene complex on chromosome 1p36 in childhood neuroblastoma. Nat Genet, 7: 370–375.

    CAS  PubMed  Google Scholar 

  26. Lapointe, J., Lachance, Y. & Labrie, C. (1996). A p18 mutant defective in cdk6 binding in human breast cancer cells. Cancer Res, 56: 4586–4589.

    CAS  PubMed  Google Scholar 

  27. Lees, J. A., Saito, M., Vidal, M., Valentine, M., Look, T., Harlow, E., Dyson, N. & Helin, K. (1993). The retinoblastoma protein binds to a family of E2F transcriptional factors. Mol Cell Biol, 13: 7813–7825.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Mantel, N. (1960). Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50: 163–170.

    Google Scholar 

  29. Mathew, C. G. P., Smith, B. A., Thorpe, K., Wong, Z., Royle, N. J., Jeffreys, A. J. & Ponder, B. A. J. (1987). Deletion of genes on chromosome 1 in endocrine neoplasia. Nature, 328: 524–526.

    CAS  PubMed  Google Scholar 

  30. Mathew, S., Murty, V. V., Bosl, G. J. & Chaganti, R. S. (1994). Loss of heterozygosity identifies multiple sites of allelic deletions on chromosome 1 in human male germ cell tumors. Cancer Res, 54: 6265–6269.

    CAS  PubMed  Google Scholar 

  31. Miller, S. A., Dykes, D. D. & Polesky, H. F. (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acids Res, 16: 1215

    CAS  PubMed  Google Scholar 

  32. Modi, W. S., Farrar, W. L. & Howard, O. M. Z. (1995). Confirmed assignment of a novel human tyrosine kinase gene (JAK1A) to 1p32.3–31.3 by non isotopic in situ hybridization. Cytogenet Cell Genet, 69: 232–234.

    CAS  PubMed  Google Scholar 

  33. Munn, K. E., Walker, R. A. & Varley, J. M. (1995). Frequent alterations of chromosome 1 in ductal carcinoma in situ of the breast. Oncogene, 10: 1653–1657.

    CAS  PubMed  Google Scholar 

  34. Ogunbiyi, O. A., Goodfellow, P. J., Gagliardi, G., Swanson, P. E., Birnbaum, E. H., Fleshman, J. W., Kodner, I. J. & Moley, J. F. (1997). Prognostic value of chromosome 1p allelic loss in colon cancer. Gastroenterology, 113: 761–766.

    CAS  PubMed  Google Scholar 

  35. Ozawa, K., Dean, F. B., Chen, M., Lee, S. H., Shiratori, A., Murakami, Y., Sakura, T., Hurwitz, J. & Eki, T. (1993). Mapping of the 70 kDa, 34 kDa, and a 11 kDa subunit of the human multimeric single-stranded DNA binding protein /hSSB/RPA) to chromosome bands 17p13, 1p35–p36.1, and 7p21–p22. Cell Struct Funct, 18: 221–230.

    CAS  PubMed  Google Scholar 

  36. Praml, C., Savelyeva, L., Le Paslier, D., Siracusa, L. D., Buchberg, A. M., Schwab, M. & Amler, L. C. (1995). Human homologue of a candidate for the MOM1 locus, the secretory type II phospholipase A2 (PLA2S-II), maps to 1p35–36.1/D1S199. Cancer Res, 55: 5504–5506.

    CAS  PubMed  Google Scholar 

  37. Ragnarsson, G., Sigurdsson, A., Eiriksdottir, G., Barkardottir, R. B., Jonasson, J. G. & Ingvarsson, S. (1996). Loss of heterozygosity at chromosomes 1p in human breast cancer – association with high S-phase, reduced patients survival, and deletions at other chromosome regions. Int J Oncol 9: 731–736.

    CAS  PubMed  Google Scholar 

  38. Rasio, D., Murakumo, Y., Robbins, D., Roth, T., Silver, A., Negrini, M., Schmidt, C., Burczak, J., Fishel, R. & Croce, C. M. (1997). Characterisation of the human homologue of RAD54 — a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors. Cancer Res 57: 2378–2383.

    CAS  PubMed  Google Scholar 

  39. Saito, T., Seki, N., Matsuda, Y., Kitahara, M., Murata, M., Kanda, N., Nomura, N., Yamamoto, T. & Hori, T. A. (1995). Identification of the human ERK gene as a putative receptor tyrosine kinase and its chromosomal localisation to 1p36.1: a comparative mapping of human, mouse, and rat chromosomes. Genomic, 26: 382–384.

    CAS  Google Scholar 

  40. Smith, S. A., Easton, D. F., Evans, D. G. & Ponder, B. A. (1992). Allele losses in the region 17q12–21 in familial breast and ovarian cancer involve the wild-type chromosome. Nature Genet, 2: 128–131.

    CAS  PubMed  Google Scholar 

  41. Speleman, F., Van Camp, G. & Van Roy, N. (1996). Reassignment of MYCL1 to human chromosome 1p34.3 by fluorescence in situ hybridization. Cytogenet Cell Genet, 72: 189–190.

    CAS  PubMed  Google Scholar 

  42. Steenman, M., Redeker, B., de Meulemeester, M., Wiesmeijer, K., Voute, P. A., Westerveld, A., Slater, R. & Mannens, M. (1997). Comparative genomic hybridization analysis of Wilms tumor. Cytogenet Cell Genet 77: 296–303.

    CAS  PubMed  Google Scholar 

  43. Stock, C., Ambros, I. M., Lion, T., Haas, O. A., Zoubek, A., Gadner, H. & Ambros, P. F. (1994). Detection of numerical and stuctural chromosome abnormalities in paediatric germ cell tumors by means of interphase cytogenetics. Genes Chromosomes Cancer, 11: 40–50.

    CAS  Google Scholar 

  44. Sulman, E. P., Tang, X. X., Allen, C., Biegel, J. A., Pleasure, D. E., Brodeur, G. M. & Ikegaki, N. (1997). ECK, a human EPH-related gene maps to 1p36.1, a common region of alteration in human cancer. Genomics, 40: 371–374.

    CAS  PubMed  Google Scholar 

  45. Taguchi, T., Jhanwar, S. C., Siegfried, J. M., Keller, S. M. & Testa, J. R. (1993). Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q and 9p in human malignant mesothelioma. Cancer Res, 53: 4349–4355.

    CAS  PubMed  Google Scholar 

  46. Tanaka, K., Yanoshita, R., Konishi, M., Oshimura, M., Maeda, Y., Mori, T. & Miyaki, M. (1993). Suppression of tumorigenicity in human colon carcinoma cell by introduction of normal chromosome 1p36 region. Oncogene, 8: 2253–2258.

    CAS  PubMed  Google Scholar 

  47. Vargas, M. P., Zhuang, Z., Wang, C., Vortmeyer, A., Linehan, W. M. & Merino, M. J. (1997). Loss of heterozygosity on the short arm of chromosomes 1 and 3 in sporadic pheochromocytoma and extra-adrenal paraganglioma. Hum Pathol, 28: 411–415.

    CAS  PubMed  Google Scholar 

  48. Volpi, E. V., Romani, M. & Siniscalco, M. (1994). Subregional mapping of the human lymphocyte-specific protein tyrosine kinase gene (LCK) to 1p35–p34.3 and its position relative to the 1p marker D1S57. Cytogenet Cell Genet 67: 187–189.

    CAS  PubMed  Google Scholar 

  49. Vorobyov, E., Mertsalov, I., Dockhorn-Dwoeniczak, B., Dwoeniczak, B. & Horst, J. (1997). The genomic organization and the full coding region of the human PAX7 gene. Genomics 45: 168–174.

    CAS  PubMed  Google Scholar 

  50. White, P. S., Maris, J. M., Beltinger, C., Sulman, E., Marshall, H. N., Fujimori, M., Kaufman, B. A., Biegel, J. A., Allen, C., Hilliard, C., Valentine, M. B., Look, A. T., Enomoto, H., Sakiyama, S. & Brodeur, G. M. (1995). A region of consistent deletion in neuroblastoma maps within human chromosome 1p36.2–36.3. Proc Natl Acad Sci USA 92: 5520–5524.

    CAS  PubMed  Google Scholar 

  51. Wu, G. S., Burns, T. F., McDonald, E. R., Jiang, W., Meng, R., Krantz, I. D., Kao, G., Gan, D. D., Zhou, J. Y., Muchel, R., Hamilton, S. R., Spinner, N. B., Markowitz, S., Wu, G. & el-Deiry, W. S. (1997). Killer/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet 17: 141–143.

    CAS  Google Scholar 

  52. Yamamoto, K., Kobayashi, H., Miura, O., Hirosawa, S. & Miyasaka, N. (1997). Assignment of IL12RB1 and IL12RB2, interleukin-12 receptor beta1 and beta2 chains, to human chromosome 19 band p13.1 and chromosome 1 band p31.2, respectively, by in situ hybridization. Cytogenet Cell Genet 77: 257–258.

    CAS  PubMed  Google Scholar 

  53. Yeh, S. H., Chen, P. J., Chen, H. L., Lai, M. Y., Wang, C. C. & Chen, D. S. (1994). Frequent genetic alterations at the distal region of chromosome 1p in human hepatocellular carcinomas. Cancer Res 54: 4188–4192.

    CAS  Google Scholar 

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Ragnarsson, G., Eiriksdottir, G., Johannsdottir, J. et al. Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival. Br J Cancer 79, 1468–1474 (1999). https://doi.org/10.1038/sj.bjc.6690234

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Keywords

  • cancer
  • chromosome 1p
  • loss of heterozygosity
  • survival statistics
  • tumour-suppressor gene

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