Specific Chromosome Defect Associated with Human Small-Cell Lung Cancer: Deletion 3p(14-23)

Whang‐Peng, J.; Kao-Shan, Chien Song; Lee, E. C.; Bunn, Paul A.; Carney, Desmond N.; Gazdar, Adi F.; Minna, John D.

doi:10.1126/science.6274023

Cited by 415 publications

(119 citation statements)

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“…A high frequency of chromosomal aberrations involving chromosome 3p has been reported in HNSCC (Cowan et al, 1992;Heo et al, 1989), small-cell lung cancer (Whang-Peng et al, 1982), and esophageal carcinomas (Whang-Peng et al, 1990) by cytogenetic analysis. The observation of similar genetic changes in these three tumors and their common association with tobacco use (Franceschi et al, 1990) (Maestro et al, 1993;Wu et al, 1994), suggesting the presence of potential tumor suppressor loci.…”

Section: Discussionmentioning

confidence: 99%

Frequent Allelic Imbalance and Loss of Protein Expression of the DNA Repair Gene hOGG1 in Head and Neck Squamous Cell Carcinoma

Fan

Liu

Huang

et al. 2001

Laboratory Investigation

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SUMMARY:Reactive oxygen species produced by aerobic cellular metabolism or through exposure to environmental carcinogens can cause oxidative DNA damage by generating DNA base lesions and strand breakage. Prime among these base lesions is the conversion of guanine to 8-oxoguanine. Among 20 or so oxidative DNA base lesions, 8-oxoguanine is the most abundant and is critical in terms of mutagenesis because it is capable of mispairing with adenine, which, if not sufficiently repaired, may lead to G:C to T:A transversion upon DNA replication. The gene encoding human 8-oxoguanine DNA glycosylase 1 (hOGG1), capable of excision repair of 8-oxoguanine, has been recently cloned, characterized, and mapped to the short arm of chromosome 3 (3p25-26), a region showing frequent loss of heterozygosity (LOH) in head and neck squamous cell carcinoma (HNSCC). In the present study, we developed a tissue microdissection approach designed for use with formalin-fixed, paraffin-embedded specimens which is capable of detecting and characterizing the hOGG1 allelic loss using two highly informative, intragenic single nucleotide polymorphisms. Among 45 cases of HNSCC, 18 cases were informative. We analyzed these 18 cases and found that 11 showed evidence of hOGG1 allelic loss. By immunohistochemical staining on a total of 71 HNSCC cases using a commercially available anti-hOGG1 antibody, we showed that hOGG1 gene expression was markedly suppressed in up to 38% of the cases. The frequent allelic imbalance and suppression of the hOGG1 gene thus imply that repair for oxidative DNA damages may be relevant in future studies on head and neck squamous carcinogenesis. (Lab Invest 2001, 81:1429 -1438.H ead and neck tumors are a heterogeneous group of neoplasms that display a wide range of biologic behaviors. In the United States, excluding those from skin, central nervous system, eye, thyroid and lymph nodes, tumors of the head and neck account for 5% of the total cancer burden.Of all head and neck tumors, 80% to 90% are squamous cell carcinoma (SCC). The strong association with tobacco and alcohol use makes head and neck squamous cell carcinoma (HNSCC) one of the most preventable malignant diseases (Blot et al, 1988;Franceschi et al, 1990). Basic research on HNSCC has been largely neglected because of the tumor's rarity. However, there are approximately 50,000 new cases of HNSCC in the United States annually (Vokes et al, 1993) and the incidence is expected to climb as a result of the increasing number of female and adolescent smokers (Centers for Disease Control, 1990). In addition, despite the great emphasis on early detection and the efforts to improve multimodality treatment management, 5-year survival rate for HNSCC patients does not exceed 50% (Ries et al, 1990). The pressing epidemiologic problem and the lack of effective management for patients with HNSCC thus strengthen the need for more extensive research on HNSCC at the molecular and genetic levels.Previous studies have identified a number of genetic abnormalities in HNSCC, including no...

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Section: Discussionmentioning

confidence: 99%

Frequent Allelic Imbalance and Loss of Protein Expression of the DNA Repair Gene hOGG1 in Head and Neck Squamous Cell Carcinoma

Fan

Liu

Huang

et al. 2001

Laboratory Investigation

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“…Lung cancers are broadly classi®ed into two groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), the latter being divided into the major histological subtypes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Losses of heterozygosity (LOH) on chromosome arms 3p, 9p, 13q and 17p are among the most frequent alterations in lung tumors (Whang-Peng et al, 1982;Yokota et al, 1987;Naylor et al, 1987;Hibi et al, 1992;Kohno and Yokota, 1999;Girard et al, 2000). However, only a limited number of tumor suppressor genes have been identi®ed as potential targets for chromosomal deletion events in these tumors.…”

Section: Introductionmentioning

confidence: 99%

The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas

2001

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Loss of heterozygosity at 3p21.3 occurs in more than 90% of small cell lung carcinomas (SCLCs). The Ras association domain family 1 (RASSF1) gene cloned from the lung tumor suppressor locus 3p21.3 consists of two major alternative transcripts, RASSF1A and RASSF1C. Epigenetic inactivation of isoform A (RASSF1A) was observed in 40% of primary non-small cell lung carcinomas and in several tumor cell lines. Transfection of RASSF1A suppressed the growth of lung cancer cells in vitro and in nude mice. Here we have analysed the methylation status of the CpG island promoters of RASSF1A and RASSF1C in primary SCLCs. In 22 of 28 SCLCs (=79%) the promoter of RASSF1A was highly methylated at all CpG sites analysed. None of the SCLCs showed evidence for methylation of the CpG island of RASSF1C. The results suggest that hypermethylation of the CpG island promoter of the RASSF1A gene is associated with SCLC pathogenesis.

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“…The most frequently reported genetic abnormality in SCLC is deletion of material from chromosome 3p. Whang-Penn et al 4 first described this consistent chromosomal abnormality in SCLC cell lines by conventional karyotyping and subsequent comparative genomic hybridization (CGH) and loss of heterozygosity analysis of SCLC tumours have confirmed the prevalence of chromosome 3p abnormalities. 5,6 Three distinct regions of loss have been identified at 3p21.3, 3p12 and 3p25, suggesting the presence of multiple tumour suppressor gene on chromosome 3.…”

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confidence: 96%

Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

Ashman

Brigham

Cowen

et al. 2002

Intl Journal of Cancer

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Small cell lung cancer (SCLC) is a major cause of cancer related morbidity and mortality. Karyotypic studies have revealed numerous chromosomal aberrations in most SCLC however, classical G-banding analysis is unable to fully characterise complex marker chromosomes. Recent developments in molecular cytogenetics now allow accurate identification of the chromosomal components of complicated rearrangements. We have applied the technique of multicolour fluorescence in situ hybridization (M-FISH) in combination with comparative genomic hybridization (CGH) to the analysis of 5 SCLC cell lines and 1 primary tumour specimen to characterise the chromosomal abnormalities. CGH analysis identified many similarities between specimens, with frequent DNA copy number decreases on chromosomes 3p, 5q, 10, 16q, 17p and frequent gains on 3q, 1p, 1q and 14q. In contrast, M-FISH analysis revealed a large number of structural abnormalities, with each specimen demonstrating an individual pattern of chromosomal translocations. Forty different translocations were identified with the vast majority (39) being unbalanced. Chromosome 5 was the most frequently rearranged chromosome (9 translocations) followed by chromosomes 2, 10 and 16 (6 translocations each). Further investigation of these frequently involved chromosomes is warranted to establish whether consistent break points are involved in these translocations, causing dysregulation of specific genes that are crucial for tumour progression and secondly to identify the affected genes.

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Specific Chromosome Defect Associated with Human Small-Cell Lung Cancer: Deletion 3p(14-23)

Cited by 415 publications

References 3 publications

Frequent Allelic Imbalance and Loss of Protein Expression of the DNA Repair Gene hOGG1 in Head and Neck Squamous Cell Carcinoma

Frequent Allelic Imbalance and Loss of Protein Expression of the DNA Repair Gene hOGG1 in Head and Neck Squamous Cell Carcinoma

The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas

Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

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