High-throughput SNP/CGH approaches for the analysis of genomic instability in colorectal cancer

Brenner, Bruce M.; Rosenberg, Daniel W.

doi:10.1016/j.mrfmmm.2010.04.002

Cited by 19 publications

(14 citation statements)

References 45 publications

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“…Thus, it is likely that different tumors should vary in characteristics by several clinical aspects such as ability to metastasize and generate local recurrence. Accordingly, genomic DNA from both recurrent and non-recurrent rectal tumors in the present study showed aberrations in DNA areas that have previously been described to be frequently involved in colorectal carcinogenesis [e.g., on chromosomes 5, 8, 13, 17, 18 and 20 (11)(12)(13)(14)]. Interestingly, the copy number gains and losses were generally less pronounced in the present tumors prone to local recurrence; an observation which may not be expected in the light of numerous reports on the relationship between copy number gains and poor prognosis in colon carcinomas.…”

Section: Discussionsupporting

confidence: 64%

“…2, several DNA areas were significantly affected in both recurrent and nonrecurrent tumors, assessed by CGH-array analysis (p<0.05). Many of these affected regions are known to be involved in colorectal carcinogenesis, e.g., on chromosomes 5, 8, 13, 17, 18 and 20 (11)(12)(13)(14). However, DNA aberrations seemed overall more pronounced in DNA from non-recurrent tumors.…”

Section: Resultsmentioning

confidence: 99%

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Genomic CGH-assessed structural DNA alterations in rectal carcinoma as related to local recurrence following primary operation for cure

Kodeda

Asting

Lönnroth

et al. 2012

International Journal of Oncology

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Abstract. Several factors determine overall outcome and possible local recurrence after curative surgery for rectal carcinoma. Surgical performance is usually believed to be the most pertinent factor, followed by adjuvant oncological treatment and tumor histopathology. However, chromosomal instability is common in colorectal cancer and tumor clones are assumed to differ in aggressiveness and potential of causing local recurrence. The aim of this study was, therefore, to evaluate if genetic alterations in primary rectal carcinoma are predictive of local recurrences. A large clinical database with linked bio-bank allowed for careful matching of two patient groups (R0) resected for rectal carcinoma. One group had developed early, isolated local recurrences and the other group seemed cured after 93 months follow-up. DNA from the primary tumors was analysed with array-CGH (comparative genomic hybridization) including 55,000 genomic probes. DNA from all primary tumors in both groups displayed previously reported and well-recognised DNA aberrations in colorectal carcinoma. Significant copy number gains were confirmed in the 4q31.1-31.22 region in DNA from tumors with subsequent local recurrence. Twenty-two affected genes in this region code for products with high relevance in tumor biology (p53 regulation, cell cycle activity, transcription). DNA from rectal carcinoma displayed well-known aberrations as described for colon carcinoma with no obvious prediction of local rectal recurrence. Gains in the 4q31.1-31.22 DNA region are highly potential for local recurrence despite R0 resection to be confirmed in larger patient materials. IntroductionColorectal cancer is the third most common malignancy in Europe and the USA (1,2). The treatment of patients with rectal cancer has improved significantly the past decades, where meticulous surgery with clear resection margins is important for cure. Besides improved surgery, preoperative radiotherapy and chemoradiotherapy add to improved treatment results. However, local recurrence after resection of rectal cancer is still a substantial clinical problem. Dedicated centers report local recurrence rates in selected series of less than 4% but population-based results are rather close to 10% (3-6). Such treatment failures lead to severe, often intractable symptoms and premature death in the majority of patients (7,8). Thus, it is important to gain further knowledge of factors that determine increased risks for local recurrence following primary operation of rectal carcinoma aimed at cure. The present study evaluates whole genomic array-CGH (comparative genomic hybridization) analysis comparing more than 55,000 DNA sites in primary rectal tumors from patients with tissue in a large bio-bank with linked clinical information. DNA from tumors that recurred locally and non-recurrent tumors were analyzed with the aim to link structural DNA-alterations to isolated local recurrence following R0-resections. Materials and methods Selection of patients.The Sahlgrenska University Hospital is a non-...

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Section: Discussionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Genomic CGH-assessed structural DNA alterations in rectal carcinoma as related to local recurrence following primary operation for cure

Kodeda

Asting

Lönnroth

et al. 2012

International Journal of Oncology

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“…Human esophageal cancer cell lines (TE-1, TE-4, TE-6, TE-8, TE-9, TE-10, TE-11, TE-14, and TE-15) were obtained from the Institute of Development, Aging, and Cancer, Tohoku University (Sendai, Japan) and were cultured in a medium supplemented with 10% FBS in 5% CO 2 atmosphere at 37 C.…”

Section: Cell Linesmentioning

confidence: 99%

LINE-1 Hypomethylation, DNA Copy Number Alterations, and CDK6 Amplification in Esophageal Squamous Cell Carcinoma

Baba

Watanabe

Murata

et al. 2014

Clinical Cancer Research

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Purpose: Global DNA hypomethylation plays a crucial role in genomic instability and carcinogenesis. DNA methylation of the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level, and is attracting interest as a useful marker for predicting cancer prognosis. Our previous study using more than 200 esophageal squamous cell carcinoma (ESCC) specimens demonstrated the significant relationship between LINE-1 hypomethylation and poor prognosis. However, the mechanism by which LINE-1 hypomethylation affects aggressive tumor behavior has yet to be revealed.Experimental Design: To examine the relationship between LINE-1 hypomethylation and DNA copy number variations, we investigated LINE-1-hypomethylated and LINE-1-hypermethylated ESCC tumors by comparative genomic hybridization array.Results: LINE-1-hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6. LINE-1 methylation levels were significantly associated with CDK6 mRNA and CDK6 protein expression levels in ESCC specimens. In our cohort of 129 patients with ESCC, cases with CDK6-positive expression experienced worse clinical outcome compared with those with CDK6-negative expression, supporting the oncogenic role of CDK6 in ESCC. In addition, we found that the prognostic impact of LINE-1 hypomethylation might be attenuated by CDK6 expression.Conclusion: LINE-1 hypomethylation (i.e., global DNA hypomethylation) in ESCC might contribute to the acquisition of aggressive tumor behavior through genomic gains of oncogenes such as CDK6. Clin Cancer Res; 20(5); 1114-24. Ó2014 AACR.

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“…Massively parallel sequencing technology enables rapid and sensitive sequencing, thus allowing the simultaneous identification of mutations from multiple patient samples in multiple genes potentially important for tumor development (15,16). The assessment was conducted on banked tissue samples [formalin-fixed paraffinembedded (FFPE)] that were previously assessed for KRAS codons 12 and 13 from patients with mCRC enrolled in a randomized phase III study (the 408 study; ref.…”

Section: Introductionmentioning

confidence: 99%

Massively Parallel Tumor Multigene Sequencing to Evaluate Response to Panitumumab in a Randomized Phase III Study of Metastatic Colorectal Cancer

Peeters

Oliner

Parker³

et al. 2013

Clinical Cancer Research

216

168

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Purpose: To investigate whether EGF receptor (EGFR) pathway mutations predicted response to monotherapy with panitumumab, an anti-EGFR monoclonal antibody, in a randomized phase III study of metastatic colorectal cancer.Experimental Design: Using massively parallel multigene sequencing, we analyzed 320 samples for 9 genes, with multigene sequence data from 288 (90%) samples.Results: Mutation rates were:, and CTNNB1 (2%). In the randomized study and open-label extension, 22 of 138 (16%) wild-type KRAS (codons 12/13/61) patients versus 0 of 103 mutant KRAS (codons 12/13) patients had objective responses. Of 6 mutant KRAS (codon 61) patients, 1 with a Q61H mutation achieved partial response during the extension. Among wild-type KRAS (codons 12/13/61) patients, 0 of 9 patients with NRAS mutations, 0 of 13 with BRAF mutations, 2 of 10 with PIK3CA mutations, 1 of 9 with PTEN mutations, and 1 of 2 with CTNNB1 mutations responded to panitumumab. No patients responded to best supportive care alone. Panitumumab treatment was associated with longer progression-free survival (PFS) among wild-type KRAS (codons 12/13/61) patients [HR, 0.39; 95% confidence interval (CI), 0.28-0.56]. Among wild-type KRAS patients, a treatment effect for PFS favoring panitumumab occurred in patients with wild-type NRAS (HR, 0.39; 95% CI, 0.27-0.56) and wild-type BRAF (HR, 0.37; 95% CI, 0.24-0.55) but not mutant NRAS (HR, 1.94; 95% CI, 0.44-8.44).Conclusions: These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers.

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High-throughput SNP/CGH approaches for the analysis of genomic instability in colorectal cancer

Cited by 19 publications

References 45 publications

Genomic CGH-assessed structural DNA alterations in rectal carcinoma as related to local recurrence following primary operation for cure

Genomic CGH-assessed structural DNA alterations in rectal carcinoma as related to local recurrence following primary operation for cure

LINE-1 Hypomethylation, DNA Copy Number Alterations, and CDK6 Amplification in Esophageal Squamous Cell Carcinoma

Massively Parallel Tumor Multigene Sequencing to Evaluate Response to Panitumumab in a Randomized Phase III Study of Metastatic Colorectal Cancer

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