Translation of an STR-based biomarker into a clinically compatible SNP-based platform for loss of heterozygosity

Kissel, Heather D.; Galipeau, Patricia C.; Li, Xiaohong; Reid, Brian J.

doi:10.3233/cbm-2009-0618

Cited by 7 publications

(6 citation statements)

References 56 publications

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“…The pyrosequencing analysis of single nucleotide polymorphism (SNP) is useful to detect LOH [ 31 ], but it is not suitable for MSI detection. Highly repetitive microsatellite sequences are useful to analyze the LOH as well as MSI.…”

Section: Discussionmentioning

confidence: 99%

The gene-reduction effect of chromosomal losses detected in gastric cancers

Hong

Jeon

et al. 2010

BMC Gastroenterol

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BackgroundThe level of loss of heterozygosity (LOH) that reduces a gene dose and exerts a cell-adverse effect is known to be a parameter for the genetic staging of gastric cancers. This study investigated if the cell-adverse effect induced with the gene reduction was a rate-limiting factor for the LOH events in two distinct histologic types of gastric cancers, the diffuse- and intestinal-types.MethodsThe pathologic specimens obtained from 145 gastric cancer patients were examined for the level of LOH using 40 microsatellite markers on eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p and 18q).ResultsMost of the cancer-associated chromosomes were found to belong to the gene-poor chromosomes and to contain a few stomach-specific genes that were highly expressed. A baseline-level LOH involving one or no chromosome was frequent in diffuse-type gastric cancers. The chromosome 17 containing a relatively high density of genes was commonly lost in intestinal-type cancers but not in diffuse-type cancers. A high-level LOH involving four or more chromosomes tended to be frequent in the gastric cancers with intestinal and mixed differentiation. Disease relapse was common for gastric cancers with high-level LOH through both the hematogenous (38%) and non-hematogenous (36%) routes, and for the baseline-level LOH cases through the non-hematogenous route (67%).ConclusionsThe cell-adverse effect of gene reduction is more tolerated in intestinal-type gastric cancers than in diffuse-type cancers, and the loss of high-dose genes is associated with hematogenous metastasis.

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Section: Discussionmentioning

confidence: 99%

The gene-reduction effect of chromosomal losses detected in gastric cancers

Hong

Jeon

et al. 2010

BMC Gastroenterol

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“…To evaluate the LOH of somatic tissue at a specific locus i for a given patient, the ratio of two signal peak values was calculated and log transformed ( r i ). The p -value of the normal sample is estimated as

p_{n} = P (Z > \frac{r_{i} - m_{i}}{s_{i}}) = 1 - φ (\frac{r_{i} - m_{i}}{s_{i}})

, where Φ is the cumulative distribution function of normal (24). The p -value for LOH is estimated by 1 − p n .…”

Section: Methodsmentioning

confidence: 99%

A Comprehensive Survey of Clonal Diversity Measures in Barrett's Esophagus as Biomarkers of Progression to Esophageal Adenocarcinoma

Merlo

Shah

et al. 2010

Cancer Prevention Research

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Neoplastic progression is an evolutionary process driven by the generation of clonal diversity and natural selection on that diversity within a neoplasm. We hypothesized that clonal diversity is associated with risk of progression to cancer. We obtained molecular data from a cohort of 239 participants with Barrett's esophagus, including microsatellite shifts and loss of heterozygosity, DNA content tetraploidy and aneuploidy, methylation, and sequence mutations. Using these data, we tested all major diversity measurement methods, including genetic divergence and entropy-based measures, to determine which measures are correlated with risk of progression to esophageal adenocarcinoma. We also tested whether the use of different sets of loci and alterations to define clones (e.g., selectively advantageous versus evolutionarily neutral) improved the predictive value of the diversity indices. All diversity measures were strong and highly significant predictors of progression (Cox proportional hazards model, P < 0.001). The type of alterations evaluated had little effect on the predictive value of most of the diversity measures. In summary, diversity measures are robust predictors of progression to cancer in this cohort. Cancer Prev Res; 3(11); 1388-97. ©2010 AACR.

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“…Rapid advances in DNA technology provide opportunities for translation of 9p, 17p, and DNA content abnormalities using clinically compatible platforms such as Pyrosequencing for LOH and fluorescent in situ hybridization for copy number alterations184,186. SNP arrays permit assessment of LOH, copy number and aneuploidy on a common platform in Barrett’s oesophagus and oesophageal adenocarcinoma, demonstrating that chromosome instability was common in persons with Barrett’s oesophagus that had progressed to oesophageal adenocarcinoma as well as in advanced oesophageal adenocarcinomas155.…”

Section: Neoplastic Progression In Barrett’s Oesophagusmentioning

confidence: 99%

Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis

et al. 2010

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The public health importance of Barrett’s oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world and there are indications that the incidence of this disease is on the rise in Asian populations where it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma and data indicate that patients with Barrett’s oesophagus rarely develop oesophageal adenocarcinoma. Given that 95% of oesophageal adenocarcinoma arise in individuals without a prior diagnosis of Barrett’s oesophagus, what strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma?

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Translation of an STR-based biomarker into a clinically compatible SNP-based platform for loss of heterozygosity

Cited by 7 publications

References 56 publications

The gene-reduction effect of chromosomal losses detected in gastric cancers

The gene-reduction effect of chromosomal losses detected in gastric cancers

A Comprehensive Survey of Clonal Diversity Measures in Barrett's Esophagus as Biomarkers of Progression to Esophageal Adenocarcinoma

Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis

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