Cytogenetic findings in six posterior uveal melanomas: Involvement of chromosomes 3, 6, and 8

Sisley, Karen; Rennie, I G; Cottam, David W.; Potter, A. M.; Potter, C. W.; Rees, Robert C.

doi:10.1002/gcc.2870020307

Cited by 145 publications

(92 citation statements)

References 13 publications

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“…Loss of chromosome 3, overrepresentation of 6p, loss of 6q, amplification of 8q and overrepresentation of chromosome 8 are the most characteristic. 24,29,30 Emphasis has been given lately to the monosomy of chromosome 3 since it has been correlated with metastasis and poor prognosis. 31,32 The finding that this monosomy is the most frequent aberration suggests the presence of tumor-suppressor genes on this chromosome.…”

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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“…Shortly afterwards, my own group reported similar findings in six cases of uveal melanoma. 355 Following these initial reports it has now been established that not only do non-random chromosome abnormalities occur in uveal melanomas, but that certain abnormalities, namely loss of chromosome-3 and additional copies of the long arm of chromosome-8, arise predominantly in ciliary body tumours and are highly sensitive predictors of patient survival. [356][357][358][359] Unfortunately, to date, there are only two studies (a total of four cases), which have characterised the cytogenetic changes in iris melanomas.…”

Section: Eyementioning

confidence: 99%

Don’t it make my blue eyes brown: heterochromia and other abnormalities of the iris

Rennie

2011

Eye

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“…Indeed, studies in our own laboratory and those of others have identified specific chromosome alterations in uveal melanomas. [20][21][22][23] Moreover, it would appear that some of these changes (notably alterations of 3 and 8) correlate strongly with prognosis, [24][25][26] suggesting that these particular changes are relatively late changes in the progression to a metastatic phenotype. Thus if one accepts that uveal melanomas arise as a result of a sequence of several genetic mutations, then it is possible to speculate that some early genetic mutations may have occurred in IMLs; but that the process has arrested before a complete malignant phenotype has developed.…”

Section: Indeterminate Melanocytic Lesionsmentioning

confidence: 99%

Things that go bump in the light. The differential diagnosis of posterior uveal melanomas

Rennie

2002

Eye

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Cytogenetic findings in six posterior uveal melanomas: Involvement of chromosomes 3, 6, and 8

Cited by 145 publications

References 13 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

Don’t it make my blue eyes brown: heterochromia and other abnormalities of the iris

Things that go bump in the light. The differential diagnosis of posterior uveal melanomas

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