Dataset Information

Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates.

ABSTRACT: OBJECTIVE AND DESIGN:The goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6-9?mm) that were first identified during routine screening of patients was monitored over time by interval imaging with CT colonography. Mutations in these lesions with known growth rates were identified by targeted next-generation sequencing. The timing of mutational events was estimated using computer modelling and statistical inference considering several parameters including allele frequency and fitness. RESULTS:The mutational landscape of small polyps is varied both within individual polyps and among the group as a whole but no single alteration was correlated with growth behaviour. Polyps carried 0-3 pathogenic mutations with the most frequent being in APC, KRAS/NRAS, BRAF, FBXW7 and TP53. In polyps with two or more pathogenic mutations, allele frequencies were often variable, indicating the presence of multiple populations within a single tumour. Based on computer modelling, detectable mutations occurred at a mean polyp size of 30±35 crypts, well before the tumour is of a clinically detectable size. CONCLUSIONS:These data indicate that small colon polyps can have multiple pathogenic mutations in crucial driver genes that arise early in the existence of a tumour. Understanding the molecular pathway of tumourigenesis and clonal evolution in polyps that are at risk for progressing to invasive cancers will allow us to begin to better predict which polyps are more likely to progress into adenocarcinomas and which patients are at greater risk of developing advanced disease.

SUBMITTER: Sievers CK

PROVIDER: S-EPMC5342955 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates.

Sievers Chelsie K CK Zou Luli S LS Pickhardt Perry J PJ Matkowskyj Kristina A KA Albrecht Dawn M DM Clipson Linda L Bacher Jeffery W JW Pooler B Dustin BD Moawad Fouad J FJ Cash Brooks D BD Reichelderfer Mark M Vo Tien N TN Newton Michael A MA Larget Bret R BR Halberg Richard B RB

Gut 20160908 12

<h4>Objective and design</h4>The goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6-9 mm) that were first identified during routine screening of patients was monitored over time by interval imaging with CT colonography. Mutations in these lesions with known growth rates were identified by targeted next-generation sequencing. The timing of mutational events was estimated using computer modell ...[more]

PMID: 27609830

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Project description:Antibiotics of veterinary origin are released to agricultural fields via grazing animals or manure. Possible effects on human health through the consumption of antibiotic exposed crop plants have been intensively investigated. However, information is still lacking on the effects of antibiotics on plants themselves, particularly on non-crop species, although evidence suggests adverse effects of antibiotics on growth and performance of plants. This study evaluated the effects of three major antibiotics, penicillin, sulfadiazine and tetracycline, on the germination rates and post-germinative traits of four plant species during ontogenesis and at the time of full development. Antibiotic concentrations were chosen as to reflect in vivo situations, i.e. concentrations similar to those detected in soils. Plant species included two herb species and two grass species, and represent two crop-species and two non-crop species commonly found in field margins, respectively. Germination tests were performed in climate chambers and effects on the remaining plant traits were determined in greenhouse experiments. Results show that antibiotics, even in small concentrations, significantly affect plant traits. These effects include delayed germination and post-germinative development. Effects were species and functional group dependent, with herbs being more sensitive to antibiotics then grasses. Responses were either negative or positive, depending on plant species and antibiotic. Effects were generally stronger for penicillin and sulfadiazine than for tetracycline. Our study shows that cropland species respond to the use of different antibiotics in livestock industry, for example, with delayed germination and lower biomass allocation, indicating possible effects on yield in farmland fertilized with manure containing antibiotics. Also, antibiotics can alter the composition of plant species in natural field margins, due to different species-specific responses, with unknown consequences for higher trophic levels.

Dataset Information

Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates.

Publications

Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates.

Similar Datasets

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