16 research outputs found

    Application of Circulating Tumor DNA as a Non-Invasive Tool for Monitoring the Progression of Colorectal Cancer

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    <div><p>Background</p><p>Liquid biopsy has been proposed to be a promising noninvasive tool to obtain information on tumor progression. Through a clinical observation of a case series of 6 consecutive patients, we aim to determine the value of circulating tumor DNA (ctDNA) for monitoring the tumor burden during the treatment of colorectal cancer (CRC).</p><p>Materials and Methods</p><p>We used capture sequencing of 545 genes to identify somatic alternations in primary tumor tissues of the six CRC patients who underwent radical surgery and in 23 plasma samples collected at serial time points. We compared the mutation patterns and variant allele frequencies (VAFs) between the matched tissue and the plasma samples and evaluated the potential advantage of using ctDNA as a better tumor load indicator to detect disease relapse over carcinoembryonic antigen (CEA), cancer antigen (CA) 19–9 and imaging studies.</p><p>Results</p><p>We identified low-frequency mutations with a mean VAF of 0.88% (corresponding to a mean tumor burden of 0.20ng/mL) in the preoperative plasmas of four patients with locally advanced CRC and a subset of mutations shared by their primary tumors. The tumor loads appeared a sudden decrease upon surgery or other adjuvant treatments and then generally maintained at low levels (0.092ng/mL) until disease recurred. ctDNA increased by 13-fold when disease relapsed in one patient while the CEA and CA 19–9 levels remained normal. In this patient, all six somatic mutations identified in the preoperative plasma were detected in the recrudescent plasma again, with five mutations showing allele fraction increase.</p><p>Conclusions</p><p>We described a multi-time-point profile of ctDNA of CRC patients during the course of comprehensive treatment and observed a correlation of ctDNA level with the clinically evaluated tumor progression. This demonstrated a new strategy by analyzing the heterogeneous ctDNA to evaluate and monitor the tumor burden in the treatment and follow-up of CRC patients, with potentially better potency than conventional biomarkers.</p></div

    Genome Survey Sequencing and Genetic Background Characterization of <i>Gracilariopsis lemaneiformis</i> (Rhodophyta) Based on Next-Generation Sequencing

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    <div><p><i>Gracilariopsis lemaneiformis</i> has a high economic value and is one of the most important aquaculture species in China. Despite it is economic importance, it has remained largely unstudied at the genomic level. In this study, we conducted a genome survey of <i>Gp. lemaneiformis</i> using next-generation sequencing (NGS) technologies. In total, 18.70 Gb of high-quality sequence data with an estimated genome size of 97 Mb were obtained by HiSeq 2000 sequencing for <i>Gp. lemaneiformis</i>. These reads were assembled into 160,390 contigs with a N50 length of 3.64 kb, which were further assembled into 125,685 scaffolds with a total length of 81.17 Mb. Genome analysis predicted 3490 genes and a GC% content of 48%.</p><p>The identified genes have an average transcript length of 1,429 bp, an average coding sequence size of 1,369 bp, 1.36 exons per gene, exon length of 1,008 bp, and intron length of 191 bp. From the initial assembled scaffold, transposable elements constituted 54.64% (44.35 Mb) of the genome, and 7737 simple sequence repeats (SSRs) were identified. Among these SSRs, the trinucleotide repeat type was the most abundant (up to 73.20% of total SSRs), followed by the di- (17.41%), tetra- (5.49%), hexa- (2.90%), and penta- (1.00%) nucleotide repeat type. These characteristics suggest that <i>Gp. lemaneiformis</i> is a model organism for genetic study. This is the first report of genome-wide characterization within this taxon.</p></div

    Clinical application of ctDNA to monitor colorectal cancer in patients after surgery.

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    <p>CEA and CA 19–9 levels and tumor burden were assessed at the indicated time points in (<b>A</b>) patient 3, (<b>C</b>) patient 5, and (<b>D</b>) patient 6, who showed no recurrence; (<b>B</b>) patient 4, in whom colonoscopy and contrast-enhanced computed tomography (CT) showed recurrence. ctDNA, circulating tumor DNA; P, patient; CEA, carcinoembryonic antigen; CA 19–9, cancer antigen 19–9; W, week; M, month(s).</p

    Percentage of the genome masked as each class of transposable elements.

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    <p>Note: RepBase TEs and TE proteins were obtained, using RepeatMasker and RepeatProteinMask respectively, based on the RepBase library; De novo repeat prediction identified repetitive DNA using RepeatMasker against the <i>de novo</i> repeat library of <i>Gp. lemaneiformis</i>, which was constructed by the programs LTR-FINDER, Piler and RepeatScout; Combined TEs were the integration and filtering redundancies of the above three methods.</p
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