Allele-specific loss of heterozygosity in multiple colorectal adenomas: toward an integrated molecular cytogenetic map II

Mao, Xin; Hamoudi, Rifat; Talbot, Ian C.; Baudis, Michael

doi:10.1016/j.cancergencyto.2005.08.030

Cited by 19 publications

(14 citation statements)

References 92 publications

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“…By contrast, dosage events affecting genes that promote cancer in allele-independent manner, e.g. loss of CDKN2A or gain of MYC , were expected to display random somatic alterations of either allele [12]. To determine the presence of allele-specific changes occurring within tumors of individual patients, we performed loss of heterozygosity analyses of 45 microsatellite markers covering 14 chromosomal regions that were chosen based on the frequency of aberration as measured by aCGH and without prior knowledge of regions showing more similarity within versus across patients.…”

Section: Resultsmentioning

confidence: 98%

Germline Variation Controls the Architecture of Somatic Alterations in Tumors

et al. 2010

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Studies have suggested that somatic events in tumors can depend on an individual's constitutional genotype. We used squamous cell carcinomas (SCC) of the skin, which arise in high multiplicity in organ transplant recipients, as a model to compare the pattern of somatic alterations within and across individuals. Specifically, we performed array comparative genomic hybridization on 104 tumors from 25 unrelated individuals who each had three or more independently arisen SCCs and compared the profiles occurring within patients to profiles of tumors across a larger set of 135 patients. In general, chromosomal aberrations in SCCs were more similar within than across individuals (two-sided exact-test p-value ), consistent with the notion that the genetic background was affecting the pattern of somatic changes. To further test this possibility, we performed allele-specific imbalance studies using microsatellite markers mapping to 14 frequently aberrant regions of multiple independent tumors from 65 patients. We identified nine loci which show evidence of preferential allelic imbalance. One of these loci, 8q24, corresponded to a region in which multiple single nucleotide polymorphisms have been associated with increased cancer risk in genome-wide association studies (GWAS). We tested three implicated variants and identified one, rs13281615, with evidence of allele-specific imbalance (p-value = 0.012). The finding of an independently identified cancer susceptibility allele with allele-specific imbalance in a genomic region affected by recurrent DNA copy number changes suggest that it may also harbor risk alleles for SCC. Together these data provide strong evidence that the genetic background is a key driver of somatic events in cancer, opening an opportunity to expand this approach to identify cancer risk alleles.

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Section: Resultsmentioning

confidence: 98%

Germline Variation Controls the Architecture of Somatic Alterations in Tumors

et al. 2010

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“…In terms of cancer, LOH signifies that in tumour cells carrying a mutated allele of a tumour suppressor gene, the gene becomes fully inactivated when the cell loses a large part of the chromosome carrying the wild-type allele (http://www.ncbi.nlm.nih.gov/cancerchromosomes). LOH is traditionally used as a molecular tool to identify a tumour-suppressor gene but it also represents one of the most common molecular features of cancer cells [47, 50–52]. Previous studies have shown LOH at MS loci on chromosomes 1p, 9p, 10q, 12q, 13q, 17p, and 19 in CTCL including SS [9, 15–19, 48].…”

Section: Discussionmentioning

confidence: 99%

“…This test was carried out through a data mining experiment by using a bioinformative method developed by us [46]. In this experiment, the effect of SNP LOH detected in this study on gene expression profiling in SS cases conducted in previous studies [23, 24, 47] was tested as before [46]. The procedures were briefly described as follows.…”

Section: Methodsmentioning

confidence: 99%

“…Here each column represents one test sample and each coloured rectangular bar signifies each individual gene. The colouration of each bar indicates the expression level of individual gene, which has been reported previously [23, 24, 47] and is not the focus of this study. The separation of 6 Sézary syndrome cases (SS, left and middle) from 2 normal controls (NC, right) is clearly visible and two test groups are different.…”

Section: Figurementioning

confidence: 99%

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Integrated Genomic Analysis of Sézary Syndrome

Mao

Chaplin

Young

2011

Genetics Research International

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Sézary syndrome (SS) is a rare variant of primary cutaneous T-cell lymphoma. Little is known about the underlying pathogenesis of S. To address this issue, we used Affymetrix 10K SNP microarray to analyse 13 DNA samples isolated from 8 SS patients and qPCR with ABI TaqMan SNP genotyping assays for the validation of the SNP microarray results. In addition, we tested the impact of SNP loss of heterozygosity (LOH) identified in SS cases on the gene expression profiles of SS cases detected with Affymetrix GeneChip U133A. The results showed: (1) frequent SNP copy number change and LOH involving 1, 2p, 3, 4q, 5q, 6, 7p, 8, 9, 10, 11, 12q, 13, 14, 16q, 17, and 20, (2) reduced SNP copy number at FAT gene (4q35) in 75% of SS cases, and (3) the separation of all SS cases from normal control samples by SNP LOH gene clusters at chromosome regions of 9q31q34, 10p11q26, and 13q11q12. These findings provide some intriguing information for our current understanding of the molecular pathogenesis of this tumour and suggest the possibility of presence of functional SNP LOH in SS tumour cells.

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“…Recently, the interval-specific aberration information from the Progenetix data set and the parsing software for CGH, as well as metaphase banding-based annotations, have shown their usefulness for the delineation of genomic aberration patterns with prognostic relevance (16) and for producing tumor type-specific combined genomic imbalance maps (17,18). …”

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confidence: 99%

Allele-specific loss of heterozygosity in multiple colorectal adenomas: toward an integrated molecular cytogenetic map II

Cited by 19 publications

References 92 publications

Germline Variation Controls the Architecture of Somatic Alterations in Tumors

Germline Variation Controls the Architecture of Somatic Alterations in Tumors

Integrated Genomic Analysis of Sézary Syndrome

Online Database and Bioinformatics Toolbox to Support Data Mining in Cancer Cytogenetics

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