Assessment of genomic damage in colorectal cancer by DNA fingerprinting: prognostic applications.

Arribas, Rosa; Capellà, Gabriel; Tórtola, Silvia; Masramon, Laia; Grizzle, William E.; Perucho, Manuel; Peinado, Miguel A.

doi:10.1200/jco.1997.15.10.3230

Cited by 38 publications

(37 citation statements)

References 23 publications

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“…Other groups have demonstrated that the degree of genomic damage assessed by arbitrarily primed PCR DNA fingerprinting correlates with genotypic, phenotypic and clinical variables in colorectal cancer and may be useful in assessing prognosis in that cancer type. 38 In contrast, use of traditional PCR amplification of multiple microsatellite markers to detect microsatellite instability is laborintensive and may be marker-dependent. Although microsatellite instability has been detected in small fractions in some cancer types, e.g., lung cancer 40,41 and several forms of leukemia, 42,43 reports of the microsatellite instability phenotype in breast cancer are inconsistent.…”

Section: Resultsmentioning

confidence: 99%

Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis

Papadopoulos

Benter

Anastassiou

et al. 2002

Intl Journal of Cancer

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Some types of cancer have been associated with abnormal DNA fingerprinting. We used random amplified polymorphic DNA (RAPD) to generate fingerprints that detect genomic alterations in human breast cancer. Primers were designed by choosing sequences involved in the development of DNA mutations. Seventeen primers in 44 different combinations were used to screen a total of 6 breast cancer DNA/normal DNA pairs and 6 uveal melanoma DNA/normal DNA pairs. Forty-five percent of these combinations reliably detected quantitative differences in the breast cancer pairs, while only 18% of these combinations detected differences in the uveal melanoma pairs. Fourteen (32%) and 12 (27%) primers generated a smear or did not produce any band patterns in the first and second cases, respectively. Taking into account the ability of RAPD to screen the whole genome, our results suggest that the genomic damage in breast cancer is significantly higher than in uveal melanoma. Our study confirms other reports that the molecular karyotypes produced with random priming, called amplotypes, are very useful for assessing genomic damage in cancer. Genomic instability is a hallmark of neoplastic transformation and a herald of genomic damage. The existence of an additional type of genomic instability has been described, the microsatellite mutator phenotype pathway. Progress in molecular cancer genetics has facilitated the detection of these mutations. In the last decade, representation differential analysis and comparative genomic hybridization (CGH) were added to methods like flow cytometry, restriction fragment length polymorphisms of polymorphic minisatellite loci and allelotyping, a PCR amplification of informative microsatellite loci.Another promising approach has been introduced, arbitrarily primed PCR 1 combined with random amplified polymorphic DNA (RAPD). 2 Both PCR-based techniques, called amplotyping, use fingerprinting to quantitatively and qualitatively evaluate band alterations. 3 This random priming method allows comparison of normal and tumor tissues at a minimum of 20 -40 genome sites in a single PCR, though evidence suggests that the number of compared loci runs into the hundreds if we take into account that a gel band consists of many comigrating fragments. 4,5 It also includes internal controls and detects moderate gains of chromosomal sequences (trisomy/tetrasomy) that would otherwise escape detection.Previously, we addressed the problems of reproducibility and contamination in random priming. In the present work, we used RAPD fingerprinting to assess the genomic damage present in breast cancer and in uveal melanoma cells. For this task, we designed primers based on sequences that are supposed to play an important role in the mechanisms leading to DNA alterations. Human gene mutations appear to be caused by multiple mechanisms whose relative importance is probably governed by local primary and secondary DNA structure. 7 We have searched for consensus sequences located in the immediate vicinity of gene mutations and for "hot s...

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Section: Resultsmentioning

confidence: 99%

Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis

Papadopoulos

Benter

Anastassiou

et al. 2002

Intl Journal of Cancer

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“…This heterogeneity is probably responsible for the failure of otherwise effective therapeutic strategies (Heppner and Miller, 1998;Leith and Dexter, 1986;Vinyals et al, 1999). It is assumed that a correlation exists between increased genomic damage and malignant behavior (Arribas et al, 1997;Kern et al, 1989). Different molecular approaches have been used to quantify the extent of genomic disruption along the tumor and its association with identifiable clinical manifestations.…”

Section: Discussionmentioning

confidence: 99%

Redefining the Significance of Aneuploidy in the Prognostic Assessment of Colorectal Cancer

Risques

Marcuello

Pétriz

et al. 2001

Laboratory Investigation

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SUMMARY:The aberrant content of DNA, or aneuploidy, is a hallmark of tumor cells and may be associated with malignant potential. Based on the hypothesis that aneuploidy, as a form of genetic instability, results in an increased capability to generate cell heterogeneity, we investigated whether a comprehensive assessment of aneuploidy extent and degree might be a reliable indicator of tumor aggressiveness. DNA content was determined by flow cytometry in the infiltrating front of 131 paraffinembedded primary colorectal carcinomas collected in a prospective design. Enrichment of tumor cells by sample microdissection resulted in neoplastic cell contents above 75%. An estimate of aneuploidy, the aneuploidy index (AI), was calculated as the tumor DNA content adjusted by the percentage of diploid and aneuploid cells in G0/G1. Thirty-nine tumors were diploid, 90 hyperdiploid, and 2 hypodiploid. The mean AI in aneuploid tumors was 1.20 Ϯ 0.17 and correlated with Dukes' stage and metastasis (p Ͻ 0.05). A high AI (receiver operating characteristic curve cutoff value greater than 1.14) predicted a poorer outcome in univariate (p ϭ 0.004) and multivariate (p ϭ 0.01) analyses. Based on these results, we postulate that aneuploidy is the molecular engine of progression in a subset of colorectal cancers, in which the AI seems to be a sensible and independent gauge of malignant potential. The AI determination may have prognostic application in colorectal cancer, especially in low-grade tumors, which might benefit from coadjuvant therapies. (Lab Invest 2001, 81:307-315).

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“…Broad di erences are observed from sample to sample and also regarding the sign of the deregulation (up or down). The increased DDTF associated to advanced Dukes' stages and lymph node invasion appears as a predictable relationship due to the accumulated genomic damage that also accompanies these phenotypes (Arribas et al, 1997). Besides the correlation of a higher gene deregulation with more invasive stages, the index of di erential expression appeared to be an independent prognostic factor.…”

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confidence: 91%

“…Di erent studies have unveiled the extent of the genomic damage sustained by the tumor cell in human colorectal cancer (Kokal et al, 1986;Thein et al, 1987;Vogelstein et al, 1988;Delattre et al, 1989;Dutrillaux et al, 1995;Ried et al, 1996;Arribas et al, 1997). Genetic alterations accumulate during tumor progression and appear as a consequence of the instabilization of the genome.…”

mentioning

confidence: 99%

“…Genetic alterations accumulate during tumor progression and appear as a consequence of the instabilization of the genome. In many cases, the type and level of genomic damage has been associated to molecular and clinical parameters and its application as prognostic factor has been also propounded (Kokal et al, 1986;Kern et al, 1989;Arribas et al, 1997). Malignant transformation of the cell is also accompanied by aberrant expression of multiple genes.…”

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confidence: 99%

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Overall deregulation in gene expression as a novel indicator of tumor aggressiveness in colorectal cancer

et al. 1999

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Assessment of genomic damage in colorectal cancer by DNA fingerprinting: prognostic applications.

Abstract: The degree of genomic damage assessed by unbiased DNA fingerprinting correlates with genotypic, phenotypic, and clinical variables in colorectal carcinoma and may be useful in assessing prognosis in colorectal cancer.

Cited by 38 publications

References 23 publications

Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis

Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis

Redefining the Significance of Aneuploidy in the Prognostic Assessment of Colorectal Cancer

Overall deregulation in gene expression as a novel indicator of tumor aggressiveness in colorectal cancer

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