Diet, Lifestyle, and Genomic Instability in the North Carolina Colon Cancer Study

Satia, Jessie A.; Keku, Temitope O.; Galanko, Joseph A.; Martin, Christopher F.; Doctolero, Ryan T.; Tajima, Akihiro; Sandler, Robert S.; Carethers, John M.

doi:10.1158/1055-9965.epi-04-0486

Cited by 76 publications

(66 citation statements)

References 30 publications

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“…17,18 The blocks age ranged from 2-to 8-years old, with 85% of samples from 1999 to 2001. The following clinical criteria were provided for each FFPE specimen: cancer type, primary tumor or metastases and age of the specimen.…”

Section: Materials and Methods Ffpe Tissuementioning

confidence: 99%

RNA expression analysis of formalin-fixed paraffin-embedded tumors

Penland

Keku

Torrice

et al. 2007

Laboratory Investigation

146

120

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RNA expression analysis is an important tool in cancer research, but a limitation has been the requirement for high-quality RNA, generally derived from frozen samples. Such tumor sets are often small and lack clinical annotation, whereas formalin-fixed paraffin-embedded (FFPE) materials are abundant. Although RT-PCR-based methods from FFPE samples are finding clinical application, genome-wide microarray analysis has proven difficult. Here, we report expression profiling on RNA from 157 FFPE tumors. RNA was extracted from 2-to 8-year-old FFPE or frozen tumors of known and unknown histologies. Total RNA was analyzed, reverse-transcribed and used for the synthesis of labeled aRNA after two rounds of amplification. Labeled aRNA was hybridized to a 3 0 -based 22K spot oligonucleotide arrays, and compared to a labeled reference by two-color microarray analysis. After normalization, gene expression profiles were compared by unsupervised hierarchical clustering. Using this approach, at least 24% of unselected FFPE samples produced RNA of sufficient quality for microarray analysis. From our initial studies, we determined criteria based on spectrophotometric analyses and a novel TaqMan-based assay to predict which samples were of sufficient quality for microarray analysis before hybridization. These criteria were validated on an independent set of tumors with a 100% success rate (20 of 20). Unsupervised analysis of informative gene expression profiles distinguished tumor type and subtype, and identified tumor tissue of origin in three unclassified carcinomas. Although only a minority of FFPE blocks could be analyzed, we show that informative RNA expression analysis can be derived from selected FFPE samples.

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Section: Materials and Methods Ffpe Tissuementioning

confidence: 99%

RNA expression analysis of formalin-fixed paraffin-embedded tumors

Penland

Keku

Torrice

et al. 2007

Laboratory Investigation

146

120

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“…14,15 A second cohort of 503 patients with colon tumors were prospectively collected as part of the North Carolina Colon Cancer Study (NCCCS), a population-based, case-control study comprising 503 patients. 16 Both studies were performed under IRB approval. The MSI status of most tumors in both cohorts had been previously determined.…”

Section: Patient Selection and Data Collectionmentioning

confidence: 99%

“…The MSI status of most tumors in both cohorts had been previously determined. 7,[14][15][16] All tumors were formalin-fixed and embedded in paraffin, then sliced into 5 lm sections. A reference hematoxylin and eosin stain was performed on one cut, and on subsequent cuts, the normal and tumor tissue were determined and marked for microdissection by a single pathologist (KM), who was blinded to the results of the target gene analysis.…”

Section: Patient Selection and Data Collectionmentioning

confidence: 99%

Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers

Jung

Smith

Doctolero

et al. 2006

Intl Journal of Cancer

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High-frequency microsatellite unstable (MSI-H) colon tumors develop as a consequence of mutations at repetitive sequences in target genes. TGFBR2 and ACVR2, encoding TGFb superfamily receptors, and the proapoptotic gene BAX are frequent targets for frameshift mutation. We analyzed the effect of these mutations on survival and histology in 2 separate cohorts. Forty-eight MSI-H Dukes B2 colon tumors from a cohort of 172 patients had mutations in TGFBR2, BAX and ACVR2 correlated with patient survival. Further, 54 population-based MSI-H colon cancers of all stages from a cohort of 503 patients had mutations correlated with tumor stage, grade and size. Of 44 amplifiable MSI-H Dukes B2 tumors, 70% harbored TGFBR2, 63% BAX and only 4.5% ACVR2 mutations. While mutation alone did not influence survival, concomitant mutation of TGFBR2 and BAX was associated with an improved prognosis in Dukes B2 patients (p 5 0.05). ACVR2 mutations were more frequent in the second, populationbased cohort (stage II: 32.5%, p < 0.05). While no target gene mutation correlated with stage in this cohort, poor histological grade and large tumor volume were associated with mutant ACVR2, but not TGFBR2 or BAX mutations, and likely accounts for the lower prevalence of ACVR2 mutations in the first, well-differentiated Dukes B2 cohort. Because target gene mutations did not correlate with stage, they likely occur early in the pathogenesis of MSI-H cancers. Mutations in TGFBR2 and BAX may improve survival in MSI-H Dukes B2 patients, and mutations of ACVR2 may augment histological changes consistent with poor tumor grade that is characteristic of MSI-H colon cancers, and increase tumor size. ' 2005 Wiley-Liss, Inc.

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“…An analysis of 144 microsatellite stable (MSS) and 40 MSI colonic cancers described an increased intake of red meat as associated with increased prevalence of MSS cancers (Diergaarde, Braam, van Muijen, Ligtenberg, Kok & Kampman, 2003). However, an assessment of 437 MSS and 49 MSI colonic cancers, failed to identify a similar association with red meat and MSS status (Satia et al, 2005). Additionally, a further report, testing 238 MSS and 35 MSI colonic cancers also failed to identify red meat intake as associated with MSI or MSS status (Wu et al, 2001).…”

Section: Msi and Dietary Associationsmentioning

confidence: 99%