title: EGFR activating aberration occurs independently of other genetic aberrations or telomerase activation in adenocarcinoma of the lung.
abstract: The prognosis of lung cancer remains poor, and biological heterogeneity is largely responsible, especially in adenocarcinoma. We previously found that only one third of non-small cell lung cancer (NSCLC) but most small cell lung cancer (SCLC) tissues have strong telomerase activity, representing the difference in the history of multiple clonal selections. To reveal the genes differentially involved in telomerase activation mechanisms, we analyzed the relationship between common genetic aberrations and telomerase activity in 83 lung cancer tissues. We found that half (7 of 14) of lung adenocarcinomas with high telomerase activity showed neither TP53 nor RB1 deletion, while all squamous cell carcinomas and SCLCs with high telomerase activity showed loss of heterozygosity of at least one, if not both, of these suppressor oncogenes, indicating that these genetic aberrations are not required in activation of telomerase in a unique subset of adenocarcinoma. Furthermore, whereas the aberrations in TP53, RB1 and 1p34-pter were mutually related in 42 adenocarcinoma tissues, EGFR aberrations showed no relationship to either of them. These findings indicate that EGFR activating aberrations occur independently of other common genetic aberrations or telomerase activation mechanisms in lung adenocarcinoma, and that the distinct subset of lung adenocarcinoma with high telomerase activity without any common genetic aberrations may possibly have arisen from a telomerase-positive or telomerase-competent normal cell.
authors.affiliation: Department of Translational Cancer Research, Hiroshima University, Research Institute for Radiation Biology and Medicine, Hiroshima 734-8553, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Arifin
authors.forename: Keiko
authors.initials: K
authors.lastname: Hiyama
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Wiwien Heru
authors.initials: WH
authors.lastname: Wiyono
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nishiyama
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics*; D002869:Chromosome Aberrations; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016160:Retinoblastoma Protein / Q000235:genetics; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D019098:Telomerase; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins