Publications by authors named "Hong C Lee"

3 Publications

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Whole genomes redefine the mutational landscape of pancreatic cancer.

Nature 2015 Feb;518(7540):495-501

Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.
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http://dx.doi.org/10.1038/nature14169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523082PMC
February 2015

Dispersion and domestication shaped the genome of bread wheat.

Plant Biotechnol J 2013 Jun 24;11(5):564-71. Epub 2013 Jan 24.

School of Agriculture and Food Sciences, University of Queensland, Brisbane, QLD, Australia.

Despite the international significance of wheat, its large and complex genome hinders genome sequencing efforts. To assess the impact of selection on this genome, we have assembled genomic regions representing genes for chromosomes 7A, 7B and 7D. We demonstrate that the dispersion of wheat to new environments has shaped the modern wheat genome. Most genes are conserved between the three homoeologous chromosomes. We found differential gene loss that supports current theories on the evolution of wheat, with greater loss observed in the A and B genomes compared with the D. Analysis of intervarietal polymorphisms identified fewer polymorphisms in the D genome, supporting the hypothesis of early gene flow between the tetraploid and hexaploid. The enrichment for genes on the D genome that confer environmental adaptation may be associated with dispersion following wheat domestication. Our results demonstrate the value of applying next-generation sequencing technologies to assemble gene-rich regions of complex genomes and investigate polyploid genome evolution. We anticipate the genome-wide application of this reduced-complexity syntenic assembly approach will accelerate crop improvement efforts not only in wheat, but also in other polyploid crops of significance.
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http://dx.doi.org/10.1111/pbi.12044DOI Listing
June 2013

Bioinformatics tools and databases for analysis of next-generation sequence data.

Brief Funct Genomics 2012 Jan 19;11(1):12-24. Epub 2011 Dec 19.

Genome sequencing has been revolutionized by next-generation technologies, which can rapidly produce vast quantities of data at relatively low cost. With data production now no longer being limited, there is a huge challenge to analyse the data flood and interpret biological meaning. Bioinformatics scientists have risen to the challenge and a large number of software tools and databases have been produced and these continue to evolve with this rapidly advancing field. Here, we outline some of the tools and databases commonly used for the analysis of next-generation sequence data with comment on their utility.
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http://dx.doi.org/10.1093/bfgp/elr037DOI Listing
January 2012
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