Mutations in the retinoblastoma-related gene RB2/p130 in primary nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an endemic cancer in southern China and northern Africa, and its pathogenesis is not yet well defined at the molecular level. Although the involvement of p53 and of the retinoblastoma gene (RB/p105) in NPC has been well studied, there is paucity of mutational data regarding the retinoblastoma-related gene RB2/p130 in primary tumors and particularly in NPC. We have shown previously that RB2/p130 could be rearranged in a nasopharyngeal cell line. In the present study, we screened by single-strand conformation polymorphism and sequence analysis the retinoblastoma-related gene RB2/p130 for mutations within exons 19-22. Mutations in the RB2/p130 gene were detected in 3 of 10 primary human NPCs from Northern Africa (30%). These findings, along with previous data showing that genetic replacement of RB2/p130 restores a normal growth pathway in the nasopharyngeal cell line Hone-1, strengthen the hypothesis that genetic changes of RB2/p130 may be involved in the development and/or progression of nasopharyngeal cancer and suggest that RB2/p130 could be considered a tumor suppressor gene and may be a candidate for novel gene therapeutic approaches for NPC.

[1]  W. Hauck,et al.  Retinoblastoma-related protein pRb2/p130 and suppression of tumor growth in vivo. , 1998, Journal of the National Cancer Institute.

[2]  H. Pass,et al.  The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas , 1997, Nature Medicine.

[3]  P. Nichols,et al.  Presence of p53 mutations in primary nasopharyngeal carcinoma (NPC) in non-Asians of Los Angeles, California, a low-risk population for NPC. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[4]  N. Tommerup,et al.  Loss of the retinoblastoma protein-related p130 protein in small cell lung carcinoma. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A. Giordano,et al.  Retinoblastoma protein family in cell cycle and cancer: A review , 1996, Journal of cellular biochemistry.

[6]  A. Giordano,et al.  Genomic structure of the human retinoblastoma-related Rb2/p130 gene. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Decaprio,et al.  Role of pRb-related proteins in simian virus 40 large-T-antigen-mediated transformation , 1995, Molecular and cellular biology.

[8]  G. Lenoir,et al.  Mutations clustered in exon 5 of the p53 gene in primary nasopharyngeal carcinomas from Southeastern Asia , 1995, International journal of cancer.

[9]  J. Lin,et al.  Assessment of p53 expression in nasopharyngeal carcinoma. , 1995, Human pathology.

[10]  L. Donehower,et al.  Mice deficient in both p53 and Rb develop tumors primarily of endocrine origin. , 1995, Cancer research.

[11]  G. Condorelli,et al.  p130/pRb2 has growth suppressive properties similar to yet distinctive from those of retinoblastoma family members pRb and p107. , 1994, Cancer research.

[12]  G. Thomas,et al.  Relative efficiency of denaturing gradient gel electrophoresis and single strand conformation polymorphism in the detection of mutations in exons 5 to 8 of the p53 gene. , 1994, Oncogene.

[13]  A. Levine,et al.  p53 and E2F-1 cooperate to mediate apoptosis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Klinga-Levan,et al.  The retinoblastoma-related gene, RB2, maps to human chromosome 16q12 and rat chromosome 19. , 1993, Oncogene.

[15]  P. Barber,et al.  P53 overexpression and Epstein‐Barr virus infection in undifferentiated and squamous cell nasopharyngeal carcinomas , 1993, The Journal of pathology.

[16]  M. Ewen,et al.  Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. , 1993, Genes & development.

[17]  K. Wiman The retinoblastoma gene: role in cell cycle control and cell differentiation , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  K. Kinzler,et al.  The multistep nature of cancer. , 1993, Trends in genetics : TIG.

[19]  N. Colburn,et al.  Nasopharyngeal carcinoma shows no detectable retinoblastoma susceptibility gene alterations. , 1993, Oncogene.

[20]  A. Bradley,et al.  Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis , 1992, Nature.

[21]  W. Chen,et al.  Nasopharyngeal carcinoma and retinoblastoma gene expression. , 1992, Laboratory investigation; a journal of technical methods and pathology.

[22]  L. Donehower,et al.  Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours , 1992, Nature.

[23]  W. Blattner,et al.  Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li–Fraumeni syndrome , 1990, Nature.

[24]  H. Bartsch,et al.  Volatile nitrosamine levels and genotoxicity of food samples from high‐risk areas for nasopharyngeal carcinoma before and after nitrosation , 1989, International journal of cancer.

[25]  M. Oren,et al.  Wild-type p53 can inhibit oncogene-mediated focus formation. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[26]  D. Ledbetter,et al.  Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. , 1989, Science.

[27]  B. Henderson,et al.  Cantonese-style salted fish as a cause of nasopharyngeal carcinoma: report of a case-control study in Hong Kong. , 1986, Cancer research.

[28]  B. Christensson,et al.  Induction of nasal and nasopharyngeal tumours in Sprague-Dawley rats fed with Chinese salted fish. , 1994, Acta oto-laryngologica.

[29]  P. Levine,et al.  Etiology of nasopharyngeal carcinoma: a review. , 1993, Epidemiologic reviews.

[30]  M. Stratton The p53 gene in human cancer. , 1992, European journal of cancer.

[31]  N. Raab-Traub Epstein-Barr virus and nasopharyngeal carcinoma. , 1992, Seminars in cancer biology.