Telomere length assessment in tissue sections by quantitative FISH: Image analysis algorithms

O'Sullivan, Jacintha; Finley, Jennifer C.; Risques, Rosa Ana; Shen, Wen Tang; Gollahon, Katherine A.; Moskovitz, Alexander H.; Gryaznov, Sergei M.; Harley, Calvin B.; Rabinovitch, Peter S.

doi:10.1002/cyto.a.20006

Cited by 75 publications

(66 citation statements)

References 34 publications

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“…1B). The epithelial/stromal telomere ratio, indicative of relative epithelial telomere length, yielded the most consistent and reproducible measurements, presumably because the stromal cells provide an internal control for the epithelial measurement in each image, making the analysis independent of variations in staining and tissue processing (34). Figure 2 summarizes the results obtained in each histologic group in the study.…”

Section: Resultsmentioning

confidence: 84%

“…Telomere assessment by quantitative FISH was done as described previously (26). Telomere FISH image analysis was done as described previously (34). In brief, the DNA image plane was segmented using a watershed algorithm and the nuclei thus identified were manually indicated by the operator as belonging to either epithelial or stromal categories.…”

Section: Methodsmentioning

confidence: 99%

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Chromosomal Instability in Barrett's Esophagus Is Related to Telomere Shortening

Finley¹,

Reid

Odze

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Barrett's esophagus is a useful model for the study of carcinogenesis, as the metaplastic columnar epithelium that replaces squamous esophageal epithelium is at elevated risk for development of adenocarcinoma. We examined telomere length and chromosomal instability (CIN) in Barrett's esophagus biopsies using fluorescence in situ hybridization. To study CIN, we selected centromere and locus-specific arm probes to chromosomes 17/17p (p53), 11/11q (cyclin D1), and 9/9p (p16 INK4A), loci reported to be involved in early stages of Barrett's esophagus neoplasia. Telomere shortening was observed in Barrett's esophagus epithelium at all histologic grades, whereas CIN was highest in biopsies with dysplastic changes; there was, however, considerable heterogeneity between patients in each variable. Alterations on chromosome 17 were strongly correlated with telomere length (r = 0.55; P < 0.0001) and loss of the 17p arm signal was the most common event. CIN on chromosome 11 was also associated with telomere shortening (r =0.3; P = 0.05), although 11q arm gains were most common. On chromosome 9p, arm losses were the most common finding, but chromosome 9 CIN was not strongly correlated with telomere length. We conclude that CIN is related to telomere shortening in Barrett's esophagus but varies by chromosome. Whether instability is manifested as loss or gain seems to be influenced by the chromosomal loci involved. Because telomere shortening and CIN are early events in Barrett's esophagus neoplastic progression and are highly variable among patients, it will be important to determine whether they identify a subset of patients that is at risk for more rapid neoplastic evolution. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1451-7)

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Section: Resultsmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Chromosomal Instability in Barrett's Esophagus Is Related to Telomere Shortening

Finley¹,

Reid

Odze

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Telomere Q-FISH. Dual-color (telomere and centromere) Q-FISH was done as previously described (6,7). A minimum of 50 epithelial and stromal cells were analyzed per case to obtain an average epithelial/stromal telomere intensity (proportional to telomere length), which was calculated as the epithelial/stromal ratio (6).…”

Section: Methodsmentioning

confidence: 99%

Telomere Length in the Colon Declines with Age: a Relation to Colorectal Cancer?

O'Sullivan¹,

Risques²,

Mandelson

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Telomeres shorten with age, which may be linked to genomic instability and an increased risk of cancer. To explore this association, we analyzed telomere length in normal colorectal tissue of individuals at different ages using quantitative-fluorescence in situ hybridization (Q-FISH) and quantitative-PCR (Q-PCR). Using Q-FISH, we also examined the histologically normal epithelium adjacent to, or distant from, colon adenomas and cancers, in addition to the neoplasms. Q-FISH and Q-PCR showed that telomere length was inversely associated with age until fages 60 to 70; surprisingly, beyond this age, telomere length was positively associated with age. This association was found exclusively in epithelial, and not in stromal, cells. Peripheral blood lymphocytes showed an inverse association between telomere length and age, but without any apparent increase in telomere length in the oldest individuals. Telomere length in larger adenoma lesions (>2 cm) was significantly shorter than in normal adjacent (P = 0.004) or normal distant (P = 0.05) tissue from the same individuals. However, telomere length in histologically normal epithelium adjacent to cancers or in adenomas <2 cm was not statistically different from that of the normal distant mucosa or from normal controls, evidence that a telomere-shortening field effect was not present. We suggest that the positive association between telomere length and age in the oldest patients is a consequence of selective survival of elderly patients with long colonocyte telomeres.

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“…Later during tumorigenesis, telomerase activity is resumed, compensating the telomere erosive process while permitting continued chromosomal instability. The viability to image and quantitatively assess telomeres makes this alteration a potential diagnostic tool, particularly to characterize early or preinvasive lesions (7).…”

Section: Pancreatic Tumor Tissuementioning

confidence: 99%

Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer

Jimeno

Hidalgo

2006

Molecular Cancer Therapeutics

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The rapidly expanding knowledge of the pathogenesis of pancreatic cancer at the molecular level is providing new targets for disease characterization, early diagnosis, and drug discovery and development. Gene mutation analysis has provided insight on the pathogenesis and progression from preinvasive lesions to invasive cancer. Gene and protein expression profiling has advanced our understanding of pancreatic ductal adenocarcinoma identifying genes that are highly expressed in pancreatic cancers, providing more insight into the clinicopathologic features of pancreatic cancer, and revealing novel features related to the process of tissue invasion by these tumors. The increasing knowledge of the pathway activation profile in pancreatic cancer is yielding new targets but also new markers to select patients and guide and predict therapy efficacy. The discovery of genetic factors of which the presence predisposes pancreatic cancer to successful targeting, such as the association of BRCA2/Fanconi anemia genes defects and sensitivity to mitomycin C, will eventually lead to a more individualized treatment approach. In summary, several decades of intensive research have originated multiple factors or biomarkers that are likely to be helpful in the diagnosis, characterization, and therapy selection of pancreatic cancer patients. A deep understanding of the relative relevance of each biomarker will be key to efficiently diagnose this disease and direct our patients towards the drugs more likely to be of benefit based on their particular profile. The development of new preclinical models is of paramount importance to achieve these goals. [Mol Cancer Ther 2006;5(4):787 -96]

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Telomere length assessment in tissue sections by quantitative FISH: Image analysis algorithms

Cited by 75 publications

References 34 publications

Chromosomal Instability in Barrett's Esophagus Is Related to Telomere Shortening

Chromosomal Instability in Barrett's Esophagus Is Related to Telomere Shortening

Telomere Length in the Colon Declines with Age: a Relation to Colorectal Cancer?

Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer

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