TP53 Mutations in Nonsmall Cell Lung Cancer

The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC). The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

[1]  G. Calin,et al.  Circulating microRNAs as noninvasive biomarkers in breast cancer. , 2012, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[2]  Michael R Hamblin,et al.  CA : A Cancer Journal for Clinicians , 2011 .

[3]  V. Rotter,et al.  Understanding wild-type and mutant p53 activities in human cancer: new landmarks on the way to targeted therapies , 2011, Cancer Gene Therapy.

[4]  Yih-Leong Chang,et al.  Comparison of p53 and Epidermal Growth Factor Receptor Gene Status Between Primary Tumors and Lymph Node Metastases in Non-Small Cell Lung Cancers , 2011, Annals of Surgical Oncology.

[5]  E. Vokes,et al.  Prognostic Significance of Mucin and p53 Expression in Stage IB Non-small Cell Lung Cancer: A Laboratory Companion Study to CALGB 9633 , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[6]  V. Grinkevich,et al.  Rescue of the apoptotic-inducing function of mutant p53 by small molecule RITA. , 2010, Cell Cycle.

[7]  C. Harris,et al.  Clinical outcomes and correlates of TP53 mutations and cancer. , 2010, Cold Spring Harbor perspectives in biology.

[8]  Magali Olivier,et al.  TP53 mutations in human cancers: origins, consequences, and clinical use. , 2010, Cold Spring Harbor perspectives in biology.

[9]  Varda Rotter,et al.  When mutants gain new powers: news from the mutant p53 field , 2009, Nature Reviews Cancer.

[10]  P. Hainaut,et al.  30 years and a long way into p53 research. , 2009, The Lancet. Oncology.

[11]  E. Díaz-Rubio,et al.  Prognostic and predictive markers of benefit from adjuvant chemotherapy in early-stage non-small cell lung cancer. , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[12]  M. Baumann,et al.  Radiotherapy of lung cancer: technology meets biology meets multidisciplinarity. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[13]  J. Shih,et al.  Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[14]  G. Pfeifer,et al.  Mutational spectra of human cancer , 2009, Human Genetics.

[15]  Alexei Vazquez,et al.  The genetics of the p53 pathway, apoptosis and cancer therapy , 2008, Nature Reviews Drug Discovery.

[16]  Brian H. Dunford-Shore,et al.  Somatic mutations affect key pathways in lung adenocarcinoma , 2008, Nature.

[17]  A. Inga,et al.  PRIMA‐1 synergizes with adriamycin to induce cell death in non‐small cell lung cancer cells , 2008, Journal of cellular biochemistry.

[18]  J. Subramanian,et al.  Molecular genetics of lung cancer in people who have never smoked. , 2008, The Lancet. Oncology.

[19]  W. Klepetko,et al.  Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer. , 2008, The Journal of thoracic and cardiovascular surgery.

[20]  G. Blandino,et al.  Oncogenomic Approaches in Exploring Gain of Function of Mutant p53 , 2008, Current genomics.

[21]  Eduardo Sontag,et al.  Transcriptional control of human p53-regulated genes , 2008, Nature Reviews Molecular Cell Biology.

[22]  S. Hecht,et al.  Progress and challenges in selected areas of tobacco carcinogenesis. , 2008, Chemical research in toxicology.

[23]  L. Seymour,et al.  Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Thierry Soussi,et al.  Shaping genetic alterations in human cancer: the p53 mutation paradigm. , 2007, Cancer cell.

[25]  Yang Xu,et al.  Gain of Function of p53 Cancer Mutants in Disrupting Critical DNA Damage Response Pathways , 2007, Cell cycle.

[26]  M. Olivier,et al.  Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database , 2007, Human mutation.

[27]  A. Børresen-Dale,et al.  TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes , 2007, Oncogene.

[28]  K. Wiman,et al.  Reactivation of mutant p53: molecular mechanisms and therapeutic potential , 2007, Oncogene.

[29]  C. Prives,et al.  Regulation of p53 DNA Binding , 2007 .

[30]  C. Prives,et al.  Mutant p53 gain of function: the NF-Y connection. , 2006, Cancer Cell.

[31]  K. Wiman,et al.  Strategies for therapeutic targeting of the p53 pathway in cancer , 2006, Cell Death and Differentiation.

[32]  C. Ishioka,et al.  Locus-specific mutation databases: pitfalls and good practice based on the p53 experience , 2006, Nature Reviews Cancer.

[33]  T. Soussi.  The p53 pathway and human cancer , 2005, The British journal of surgery.

[34]  Rolf Lewensohn,et al.  The role of p53 in treatment responses of lung cancer. , 2005, Biochemical and biophysical research communications.

[35]  K. Wiman,et al.  PRIMA-1MET synergizes with cisplatin to induce tumor cell apoptosis , 2005, Oncogene.

[36]  H. Berkel,et al.  Mortality From Lung Cancer and Tobacco Smoking in Ohio (U.S.): Will Increasing Smoking Prevalence Reverse Current Decreases in Mortality? , 2005, Cancer Epidemiology Biomarkers & Prevention.

[37]  J. Ferlay,et al.  Global Cancer Statistics, 2002 , 2005, CA: a cancer journal for clinicians.

[38]  D. Lane,et al.  P53 abnormalities and outcomes in colorectal cancer: a systematic review , 2005, British Journal of Cancer.

[39]  M. Protopopova,et al.  Small molecule RITA binds to p53, blocks p53–HDM-2 interaction and activates p53 function in tumors , 2004, Nature Medicine.

[40]  F. Bray,et al.  Lung cancer mortality patterns in selected Central, Eastern and Southern European countries , 2004, International Journal of Cancer.

[41]  C. Harris,et al.  p53: 25 years after its discovery. , 2004, Trends in pharmacological sciences.

[42]  P. Bonomi,et al.  Novel treatments in non-small cell lung cancer. , 2004, Hematology/oncology clinics of North America.

[43]  C. Harris,et al.  TP53 mutation spectra and load: a tool for generating hypotheses on the etiology of cancer. , 2004, IARC scientific publications.

[44]  R. Eeles,et al.  Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. , 2003, Cancer research.

[45]  Toshihide Tsuda,et al.  The TP53 gene, tobacco exposure, and lung cancer , 2003, Human mutation.

[46]  F. Bray,et al.  Lung cancer in Europe in 2000: epidemiology, prevention, and early detection. , 2003, The Lancet. Oncology.

[47]  J. Gu,et al.  Induction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[48]  N. Tretyakova,et al.  Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers , 2002, Oncogene.

[49]  Xin Lu,et al.  Live or let die: the cell's response to p53 , 2002, Nature Reviews Cancer.

[50]  C. Harris,et al.  The IARC TP53 database: New online mutation analysis and recommendations to users , 2002, Human mutation.

[51]  Galina Selivanova,et al.  Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound , 2002, Nature Medicine.

[52]  K. Bielawski,et al.  p53 Gene status in relation to ex vivo chemosensitivity of non-small cell lung cancer , 2002, Journal of Cancer Research and Clinical Oncology.

[53]  A. Levine,et al.  The p53 functional circuit. , 2001, Journal of cell science.

[54]  M. Olivier,et al.  TP53 mutation spectrum in lung cancers and mutagenic signature of components of tobacco smoke: lessons from the IARC TP53 mutation database. , 2001, Mutagenesis.

[55]  J. Lafitte,et al.  Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. , 2001, The European respiratory journal.

[56]  C. Harris,et al.  p53 and K-ras mutations in lung cancers from former and never-smoking women. , 2001, Cancer research.

[57]  P. Hainaut,et al.  Patterns of p53 G-->T transversions in lung cancers reflect the primary mutagenic signature of DNA-damage by tobacco smoke. , 2001, Carcinogenesis.

[58]  V. Rotter,et al.  Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome. , 2000, Cancer research.

[59]  A. Levine,et al.  Surfing the p53 network , 2000, Nature.

[60]  T. Mitsudomi,et al.  Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[61]  J. Roth,et al.  Adenoviral-mediated p53 gene transfer to non-small cell lung cancer through endobronchial injection. , 2000, Chest.

[62]  S. Hussain,et al.  p53 Tumor Suppressor Gene: At the Crossroads of Molecular Carcinogenesis, Molecular Epidemiology, and Human Risk Assessment , 2000, Annals of the New York Academy of Sciences.

[63]  G. Pershagen,et al.  p53 mutations and exposure to environmental tobacco smoke in a multicenter study on lung cancer. , 2000, Cancer research.

[64]  M. Tang,et al.  Targeting of lung cancer mutational hotspots by polycyclic aromatic hydrocarbons. , 2000, Journal of the National Cancer Institute.

[65]  F. Khuri,et al.  Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[66]  M. Hollstein,et al.  p53 and human cancer: the first ten thousand mutations. , 2000, Advances in cancer research.

[67]  E. Bowman,et al.  Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. , 1999, Journal of the National Cancer Institute.

[68]  J. McLaughlin,et al.  Meta-analyses of p53 tumor suppressor gene alterations and clinicopathological features in resected lung cancers. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[69]  F. Khuri,et al.  Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer. , 1999, Journal of the National Cancer Institute.

[70]  J. Luketich,et al.  Comparison of mutations in the p53 and K-ras genes in lung carcinomas from smoking and nonsmoking women. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[71]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[72]  C. Harris,et al.  Molecular epidemiology of human cancer. , 1998, Toxicology letters.

[73]  A. Riggs,et al.  The p53 codon 249 mutational hotspot in hepatocellular carcinoma is not related to selective formation or persistence of aflatoxin B1 adducts , 1998, Oncogene.

[74]  P. Hainaut,et al.  A specific spectrum of p53 mutations in lung cancer from smokers: review of mutations compiled in the IARC p53 database. , 1998, Environmental health perspectives.

[75]  K. Takami,et al.  Immunohistochemical p53 protein status in nonsmall cell lung cancer is a promising indicator in determining in vitro chemosensitivity to some anticancer drugs , 1998, Journal of surgical oncology.

[76]  J. Minna,et al.  p53 mutations in non-small-cell lung cancers occurring in individuals without a past history of active smoking. , 1998, British Journal of Cancer.

[77]  Ken Chen,et al.  The Ink4a Tumor Suppressor Gene Product, p19Arf, Interacts with MDM2 and Neutralizes MDM2's Inhibition of p53 , 1998, Cell.

[78]  Yue Xiong,et al.  ARF Promotes MDM2 Degradation and Stabilizes p53: ARF-INK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression Pathways , 1998, Cell.

[79]  A. Levine.  p53, the Cellular Gatekeeper for Growth and Division , 1997, Cell.

[80]  Thierry Soussi,et al.  Database of p53 gene somatic mutations in human tumors and cell lines: updated compilation and future prospects , 1997, Nucleic Acids Res..

[81]  M. Tang,et al.  Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53 , 1996, Science.

[82]  W. Hong,et al.  Retrovirus–mediated wild–type P53 gene transfer to tumors of patients with lung cancer. , 1996, Nature Medicine.

[83]  C. Harris,et al.  p53 tumor suppressor gene: from the basic research laboratory to the clinic--an abridged historical perspective. , 1996, Carcinogenesis.

[84]  K. Kondo,et al.  A dose‐response relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients , 1996, Journal of surgical oncology.

[85]  E. Dmitrovsky,et al.  Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer. , 1995, Cancer research.

[86]  P. Radice,et al.  Genetic evidence for an independent origin of multiple preneoplastic and neoplastic lung lesions. , 1995, Cancer research.

[87]  J. Roth,et al.  Therapeutic effect of a retroviral wild-type p53 expression vector in an orthotopic lung cancer model. , 1994, Journal of the National Cancer Institute.

[88]  T. Soussi,et al.  Analysis of the most representative tumour‐derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation. , 1994, The EMBO journal.

[89]  J. Roth,et al.  Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild-type p53 gene. , 1994, Cancer research.

[90]  P. Kleihues,et al.  p53 mutations in primary human lung tumors and their metastases , 1994, Molecular carcinogenesis.

[91]  T. Sekiya,et al.  Aberrations of the p53 tumor suppressor gene in human non-small cell carcinomas of the lung. , 1992, Cancer research.

[92]  J. Yokota,et al.  p53 mutations in human lung tumors. , 1992, Cancer research.

[93]  J. Minna,et al.  Expression of mutant p53 proteins in lung cancer correlates with the class of p53 gene mutation. , 1992, Oncogene.

[94]  S. Hirohashi,et al.  Alterations of the p53 gene are common and critical events for the maintenance of malignant phenotypes in small-cell lung carcinoma. , 1992, Oncogene.

[95]  J. Minna,et al.  High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. , 1992, Oncogene.

[96]  R. Ueda,et al.  The p53 gene is very frequently mutated in small-cell lung cancer with a distinct nucleotide substitution pattern. , 1991, Oncogene.

[97]  B. Vogelstein,et al.  p53 mutations in human cancers. , 1991, Science.

[98]  S. Naylor,et al.  Use of the single strand conformation polymorphism technique and PCR to detect p53 gene mutations in small cell lung cancer. , 1991, Oncogene.

[99]  B. Vogelstein,et al.  Mutant p53 DNA clones from human colon carcinomas cooperate with ras in transforming primary rat cells: a comparison of the "hot spot" mutant phenotypes. , 1990, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

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

[101]  J. Minna,et al.  Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. , 1990, Oncogene.

[102]  J H Ho,et al.  Worldwide epidemiological patterns of lung cancer in nonsmokers. , 1990, International journal of epidemiology.

[103]  J. Minna,et al.  p53: a frequent target for genetic abnormalities in lung cancer. , 1989, Science.

[104]  W. Blattner,et al.  A cancer family syndrome in twenty-four kindreds. , 1988, Cancer research.

[105]  P. May,et al.  Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum , 1979, Journal of virology.

[106]  A. Levine,et al.  Characterization of a 54K Dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells , 1979, Cell.

[107]  D. Lane,et al.  T antigen is bound to a host protein in SY40-transformed cells , 1979, Nature.

[108]  R. Carroll,et al.  Identification of new polypeptide species (48-55K) immunoprecipitable by antiserum to purified large T antigen and present in SV40-infected and -transformed cells. , 1979, Virology.

[109]  R. Doll,et al.  Mortality in Relation to Smoking: Ten Years' Observations of British Doctors , 1964, British medical journal.

[110]  A. Sjoerdsma,et al.  Lactation Due to Methyldopa , 1963, British medical journal.