p53 Gene Mutations as Markers of Tumor Spread in Synchronous Oral Cancers

Koch, Wayne M.; Boyle, Jay O.; Li, Mao; Hakim, John; Hruban, Ralph H.; Sidransky, David

doi:10.1001/archotol.1994.01880330029006

Cited by 45 publications

(23 citation statements)

References 12 publications

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“…2B). This is consistent with our previous observation that undetected infiltrating tumor cells can be identified in surgical margins after "complete" surgical resection with sensitive molecular techniques (6).…”

supporting

confidence: 93%

“…Detection of rare infiltrating cancer cells in histopathologic margins may have great impact on current surgical practice (6). Because the primary tumor is already resected in these cases, rapid screening of tumor DNA can provide a single marker for detection of these infiltrating tumor cells.…”

Section: Assay Sensitivity An Obvious Problem In Screening Clinicalmentioning

confidence: 99%

“…Recently, we reported a molecular diagnostic approach based on the detection of clonal oncogene mutations in urine, stool, and sputum (2)(3)(4)(5). This assay was employed to detect rare infiltrating tumor cells in apparently normal histopathologic margins and lymph nodes following surgical resection in patients with head and neck squamous cell carcinoma (SCC) (6,7). However, this polymerase chain reaction (PCR)-based method was limited for broad clinical application in that it required an additional cloning step and synthesis of a large number of oligomer-specific probes to detect a variety of oncogenic mutations for each tumor type (2)(3)(4)(5).…”

mentioning

confidence: 99%

“…Surgical margin DNA was scraped from slides and placed in xylene to remove excess paraffin. After centrifugation with 0.25 volume of 70%o ethanol, pellets were digested with 1% SDS/proteinase K and DNA was extracted as described (4,6).…”

mentioning

confidence: 99%

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

Lee

Tockman

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

372

204

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supporting

confidence: 93%

Section: Assay Sensitivity An Obvious Problem In Screening Clinicalmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Lee

Tockman

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

372

204

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“…The interaction between cancer cells and the ECM can modulate malignant behaviour both in vitro [2;3] and in vivo [4]. This modulation is highly relevant to human cancer because metastatic cells often remain dormant for years before emerging as tumours [5], and malignant cells can often masquerade as normal cells before emerging as a recurrence [6]. Understanding the mechanisms for this modulation of the malignant phenotype by ECM may present important clues for cancer treatment or management.…”

Section: Introductionmentioning

confidence: 99%

Template-driven gene selection procedure

Knowlton

Dozmorov

Kyker

et al. 2006

IEE Proc. Syst. Biol.

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The hierarchical clustering and statistical techniques usually used to analyze microarray data do not inherently represent the underlying biology. Herein we present a hybrid approach involving characteristics of both supervised and unsupervised learning. This approach is based on template matching in which the interaction of the variables of inherent malignancy and the ability to express the malignant phenotype are modelled. Immortalized normal urothelial cells and bladder cancer cells of different malignancy were grown in conventional two-dimensional tissue culture and in three dimensions on extracellular matrices that were either permissive or restrictive for expression of the malignant phenotype. The transcriptome represents the effects of two variables--inherent malignancy and the modulatory effect of extracellular matrix. By assigning values to each of the biological variables of inherent malignancy and the ability to express the malignant phenotype, a template was constructed that encapsulated the interaction between them. Gene expression correlating both positively and negatively with the template were observed, but when iterative correlations were carried out, the different models for the template converged to the same actual template. A subset of 21 genes was identified that correlated with two a priori models or an optimized model above the 95% confidence limits identified in a bootstrap resampling with 5,000 permutations of the data set. The correlation coefficients of expression of several genes were > 0.8. Analysis of upstream transcriptional regulatory elements (TREs) confirmed these genes were not a randomly selected set of genes. Several TREs were identified as significantly over-expressed in the sample of 20 genes for which TREs were identified, and the high correlations of several genes were consistent with transcriptional co-regulation. We suggest the template method can be used to identify a unique set of genes for further investigation. KeywordsBladder cancer; phenotype; transcriptomics; extracellular matrix; malignancy * This work was supported in part by NIH grants CA75322 (REH), DK 069808 (REH) and P20 RR1557, P20 RR17703, and P20 RR16478 (MBC) and by a grant from Cook Biotech (REH).

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