Comparative allelotype of early and advanced stage non-small cell lung carcinomas

Sekiguchi, Masayuki; Kohno, Takashi; Adachi, Jun-ichi; Okazaki, Toshio; Otsuka, Toshiyuki; Mizoguchi, Hideaki; Noguchi, Masayuki; Hirohashi, Setsuo; Yokota, Jun

doi:10.1002/(sici)1098-2264(199610)17:2<71::aid-gcc1>3.0.co;2-y

Cited by 68 publications

(47 citation statements)

References 14 publications

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“…Detailed information on these cell lines can be obtained upon request. High-molecular-weight DNA was prepared from tumors and adjacent noncancerous tissues of 45 patients with SCLC or NSCLC, and from peripheral blood samples of 42 unrelated healthy indivi-duals as described previously (Shiseki et al, 1994(Shiseki et al, , 1996Baba et al, 1995). Poly(A) RNA was prepared by the Fast Track mRNA isolation kit (Invitrogen Corp.).…”

Section: Samplesmentioning

confidence: 99%

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

Kohno¹,

Shinmura

Tosaka³

et al. 1998

Oncogene

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388

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The hOGG1 gene encodes a DNA glycosylase that excises 8-hydroxyguanine (oh 8 Gua) from damaged DNA. Structural analyses of the hOGG1 gene and its transcripts were performed in normal and lung cancer cells. Due to a genetic polymorphism at codon 326, hOGG1-Ser 326 and hOGG1-Cys 326 proteins were produced in human cells. Activity in the repair of oh 8 Gua was greater in hOGG1-Ser 326 protein than in hOGG1-Cys 326 protein in the complementation assay of an E. coli mutant defective in the repair of oh 8 Gua. Two isoforms of hOGG1 transcripts produced by alternative splicing encoded distinct hOGG1 proteins: one with and the other without a putative nuclear localization signal. Loss of heterozygosity at the hOGG1 locus was frequently (15/ 23, 62.2%) detected in lung cancer cells, and a cell line NCI-H526 had a mutation leading to the formation of the transcripts encoding a truncated hOGG1 protein. However, the oh 8 Gua levels in nuclear DNA were similar among lung cancer cells and leukocytes irrespective of the type of hOGG1 proteins expressed. These results suggest that the oh 8 Gua levels are maintained at a steady level, even though multiple hOGG1 proteins are produced due to genetic polymorphisms, mutations and alternative splicing of the hOGG1 gene.

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Section: Samplesmentioning

confidence: 99%

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

Kohno¹,

Shinmura

Tosaka³

et al. 1998

Oncogene

Self Cite

388

309

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“…Additional observations include cyclin D1 overexpression in a majority of NSCLC cell lines, which may result in Rb inactivation (Schauer et al, 1994); overexpression of the tyrosine kinase growth factor receptor cerbB2/neu in 10 ± 30% of NSCLC tumors and cell lines, which correlates with a worse prognosis Weiner et al, 1990); and overexpression of bcl-2 in 10 ± 25% of NSCLC specimens, with increased survival for the subset of squamous cell carcinoma patients that had bcl-2 increased expression (Pezzela et al, 1993). Further investigations of the numerous chromosomal abnormalities found in SCLC and NSCLC, such as chromosomal gains at 1p, 3q, 5p, 7p, 8q, 12p and 19q, and chromosomal losses and loss of heterozygosity (LOH) at 1p, 1q, 3p, 5p, 5q, 8p, 9p, 10q, 13q, 15q, 17p and 18q may reveal the existence of additional oncogenes and tumor suppressors, respectively, that are involved in lung tumorigenesis (Shiseki et al, 1996;Balsara et al, 1997;Mertens et al, 1997;Petersen et al, 1997;Virmani et al, 1998). Molecular abnormalities identi®ed in lung tumors are the basis for the development of screening tests for lung cancer, such as the examination of sputum from smokers for Kras and p53 mutations (Mao et al, 1994).…”

Section: Human Lung Cancer: Molecular Characterizationmentioning

confidence: 99%

Modeling human lung cancer in mice: similarities and shortcomings

1999

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Lung cancer kills more Americans yearly than any other neoplastic process. Mortality rates have changed little over the past several decades, despite improvements in surgical techniques, radiation therapy and chemotherapy. The identi®cation of mutations in oncogenes and tumor suppressor genes in human lung tumor specimens, including K-ras, p53, p16 INK4a and Rb, o ers molecular explanations for tumor development and resistance to therapy. Mouse models of human lung cancer may advance our understanding of this disease. The examination of mice which develop lung cancer either spontaneously or due to carcinogen exposure, and the creation of mouse strains harboring the speci®c genetic mutations found in human lung cancer are among strategies being pursued.

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“…Previous studies have shown allelic loss at the 17p loci to be involved at a relatively early stage of NSCLC, 8,24,25 and its loss may be associated with the genesis of NSCLC. p53 is believed to play a role as a 'guardian' that maintains the integrity of the genome by participating in the DNA damage checkpoints in the cell cycle.…”

Section: Discussionmentioning

confidence: 96%

“…Therefore, LOH at 18q appears to have a role as late event in the metastatic progression of adenocarcinomas mixed BA and other subtypes of the lung. Shiseki et al 8 reported that loss at 18q plays an important role in the progression of NSCLC based on a comparison of stage I NSCLC and brain metastases. Lymph node metastases, most malignant portions, were shown to carry 18q deletions at even higher frequency than 5q or 17p deletions in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…However, such inferences have essentially been based on statistical arguments after analysis of a set of different tumors 6,8,9 and whether they are indeed applicable to the progression scheme in individual tumors has not been specifically addressed in regard to adenocarcinoma of the lung. An alternative approach therefore seemed to be necessary, for those relying on the statistical correlation between the frequency of each genetic alteration and histological and/or disease progression, but such an approach has rarely been taken in studies of the genetic changes in adenocarcinoma of the lung.…”

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confidence: 99%

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Topographical distribution of allelic loss in individual lung adenocarcinomas with lymph node metastases

et al. 2004

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Adenocarcinomas of the lung are characterized by morphological heterogeneity, and since carcinogenesis has been suggested to be a multistep process involving sequential accumulation of multiple genetic alterations, the morphological heterogeneity may represent a cross-sectional view of genetic alterations within individual tumors. Therefore, to elucidate whether, and which, genetic alterations accumulated in relation to morphological cancer progression, we examined 56 microdissected sites for topographical distribution of loss of heterozygosity (LOH) in 12 adenocarcinomas of the lung with bronchioloalveolar (BA) and invasive components in their primary tumors and metastases to lymph nodes. The morphological changes from noninvasive BA lesions to invasive and metastatic components were characterized by a significant rise in the prevalence of allelic losses (Po0.05). Individually, eight cases (67%) showed accumulation of genetic alterations from BA lesions to metastases. LOHs in multiple foci in one case were compared to determine whether they were shared at all tumor sites as an early event or localized in metastases as an additional event.LOHs at 5q and 17p may be crucial steps in the early phase of development to metastasis, while 18q loss may be an additional step. These findings suggested that the cancer cells in some pulmonary adenocarcinomas evolved from the BA lesions to the invasive and metastatic lesions.

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Comparative allelotype of early and advanced stage non-small cell lung carcinomas

Cited by 68 publications

References 14 publications

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

Modeling human lung cancer in mice: similarities and shortcomings

Topographical distribution of allelic loss in individual lung adenocarcinomas with lymph node metastases

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