Microsatellite alterations as clonal markers for the detection of human cancer.

Li, Mao; Lee, Dong Hoon; Tockman, Melvyn S.; Erozan, Yener S.; Askin, Frederic B.; Sidransky, David

doi:10.1073/pnas.91.21.9871

Cited by 372 publications

(221 citation statements)

References 35 publications

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“…The reason for this discrepancy is unknown. The observation that the rate of instability was three times greater in the tetranucleotides (2.0%) than in the dinucleotides (0.66%) has been reported previously (Weber and Wong, 1993;Mao et al, 1994). It would be worthwhile to investigate mononucleotide and pentanucleotide repeats to see whether this pattern continued.…”

Section: Resultssupporting

confidence: 49%

Microsatellite instability and loss of heterozygosity in mammary carcinoma and its probable precursors

Dillon

Boer²,

Papadimitriou³

et al. 1997

Br J Cancer

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Summary Microsatellite instability is a form of genetic damage that may be due to defective mismatch repair genes and may be a marker of processes leading to malignancy. We have analysed a series of epithelial hyperplasia of usual type, carcinomas in situ and invasive and metastatic carcinomas from the mammary gland on the assumption that they represent stages in the evolution of mammary carcinoma. Eight markers on chromosomes 3p, 4q, 9p, 11p, 14q, 17p, 17q and Xq were examined for microsatellite instability and loss of heterozygosity. High rates of loss on chromosomes 17p, 17q and Xq indicate that these chromosomal arms contain genes important in mammary carcinogenesis. The rate of microsatellite instability observed in this study was uniformly low, irrespective of the lesion. This implies that microsatellite instability is not a marker of malignancy in most instances of mammary neoplasia.

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Section: Resultssupporting

confidence: 49%

Microsatellite instability and loss of heterozygosity in mammary carcinoma and its probable precursors

Dillon

Boer²,

Papadimitriou³

et al. 1997

Br J Cancer

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“…Alterations in microsatellite size (microsatellite alterations) are present in many cancers, including lung carcinomas (Adachi et al, 1995;Fong et al, 1995;Mao et al, 1994;Merlo et al, 1994) and may re¯ect a form of genomic instability (Wistuba et al, 1998). We found MAs in 50% of the invasive tumors and in lesser percentages of histologically normal, preneoplastic and CIS foci.…”

Section: Discussionmentioning

confidence: 76%

“…Allelic losses at chromosomal regions 3p, 9p and 17p occur relatively early during the multistage development of invasive lung cancer (Chung et al, 1996;Hung et al, 1995;Kishimoto et al, 1995;Sundaresan et al, 1992;Thiberville et al, 1995). In addition, the occurrence of aneuploidy and microsatellite alterations (MA) is evidence of more generalized genomic instability in lung cancer and its preneoplastic lesions (Mao et al, 1994;Miozzo et al, 1996). MAs represent changes in the size of simple nucleotide repeat polymorphic microsatellite markers, resulting in altered electrophoretic mobility of one or both alleles.…”

Section: Introductionmentioning

confidence: 99%

Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma

et al. 1999

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To understand the molecular pathways involved in the pathogenesis of squamous cell lung carcinoma, we obtained DNA from 94 microdissected foci from 12 archival surgically resected tumors including histologically normal epithelium (n=13), preneoplastic lesions (n=54), carcinoma is situ (CIS) (n=15) and invasive tumors (n=12). We determined loss of heterozygosity (LOH) at 10 chromosomal regions (3p12, 3p14.2, 3p14.1-21.3, 3p21, 3p22-24, 3p25, 5q22, 9p21, 13q14 RB, and 17p13 TP53) frequently deleted in lung cancer, using 31 polymorphic microsatellite markers, including 24 that spanned the entire 3p arm. Our major ®ndings are as follows: (1) Thirty one percent of histologically normal epithelium and 42% of mildly abnormal (hyperplasia/metaplasia) specimens had clones of cells with allelic loss at one or more regions; (2) There was a progressive increase of the overall LOH frequency within clones with increasing severity of histopathological changes; (3) The earliest and most frequent regions of allelic loss occurred at 3p21, 3p22-24, 3p25 and 9p21; (4) The size of the 3p deletions increased with progressive histologic changes; (5) TP53 allelic loss was present in many histologically advanced lesions (dysplasia and CIS); (6) Analyses of 58 normal and non-invasive foci having any molecular abnormality, indicated that 30 probably arose as independent clonal events, while 28 were potentially of the same clonal origin as the corresponding tumor; (7) Nevertheless, when the allelic losses in the 30 clonally independent lesions and their clonally unrelated tumors were compared the same parental allele was lost in 113 of 125 (90%) of comparisons. The mechanism by which this phenomenon (known as allele speci®c mutations) occurs is unknown; (8) Four patterns of allelic loss in clones were found. Histologically normal or mildly abnormal foci had a negative pattern (no allelic loss) or early pattern of loss while all foci of CIS and invasive tumor had an advanced pattern. However dysplasias demonstrated the entire spectrum of allelic loss patterns, and were the only histologic category having the intermediate pattern. Our ®ndings indicate that multiple, sequentially occurring allele speci®c molecular changes commence in widely dispersed, apparently clonally independent foci, early in the multistage pathogenesis of squamous cell carcinomas of the lung.

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“…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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Microsatellite alterations as clonal markers for the detection of human cancer.

Abstract: ABSTRACT

Cited by 372 publications

References 35 publications

Microsatellite instability and loss of heterozygosity in mammary carcinoma and its probable precursors

Microsatellite instability and loss of heterozygosity in mammary carcinoma and its probable precursors

Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma

Modeling human lung cancer in mice: similarities and shortcomings

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