Unravelling genetic heterogeneity of hepatocellular carcinoma with driver genes and subclones

Integration of genetic studies in hepatocellular carcinoma (HCC) is lacking though its mortality rate has risen to the second highest. With 1186 samples from varying ethnicities, this study had collected the largest sample size to compile a catalog of HCC cancer genes with MutSigCV and 37 novel gene...

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Bibliographic Details
Main Author: Ng, Ming Hwee
Other Authors: Zhai Wei Wei
Format: Final Year Project (FYP)
Language:English
Published: 2015
Subjects:
Online Access:http://hdl.handle.net/10356/65645
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author Ng, Ming Hwee
author2 Zhai Wei Wei
author_facet Zhai Wei Wei
Ng, Ming Hwee
author_sort Ng, Ming Hwee
collection NTU
description Integration of genetic studies in hepatocellular carcinoma (HCC) is lacking though its mortality rate has risen to the second highest. With 1186 samples from varying ethnicities, this study had collected the largest sample size to compile a catalog of HCC cancer genes with MutSigCV and 37 novel genes were discovered. Further increment of sample size would be valuable to build on a complete catalog, especially for driver genes that were mutated in less than 2% of samples. The driverness index of the driver genes was investigated to decipher the sole actionable drive of a cancer gene. Most driver genes required the complementation of another driver gene in tumorgenesis. This is true for CTNNB1 and TP53, which had been mutated in more than 300 samples and for AXIN1, which had been mutated in 68 samples. The clonality analysis next, determined if driver genes were found in all or a subset of a tumor and thus whether it was an early or late event in tumor evolution. It was concluded that most driver genes occurred as an early event. The genetic landscape of driverness and clonality in driver genes was drawn out in this study to unravel intratumor genetic heterogeneity and to further understand tumor evolution.
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spelling ntu-10356/656452023-02-28T18:02:00Z Unravelling genetic heterogeneity of hepatocellular carcinoma with driver genes and subclones Ng, Ming Hwee Zhai Wei Wei School of Biological Sciences A*STAR Genome Institute of Singapore DRNTU::Science::Biological sciences Integration of genetic studies in hepatocellular carcinoma (HCC) is lacking though its mortality rate has risen to the second highest. With 1186 samples from varying ethnicities, this study had collected the largest sample size to compile a catalog of HCC cancer genes with MutSigCV and 37 novel genes were discovered. Further increment of sample size would be valuable to build on a complete catalog, especially for driver genes that were mutated in less than 2% of samples. The driverness index of the driver genes was investigated to decipher the sole actionable drive of a cancer gene. Most driver genes required the complementation of another driver gene in tumorgenesis. This is true for CTNNB1 and TP53, which had been mutated in more than 300 samples and for AXIN1, which had been mutated in 68 samples. The clonality analysis next, determined if driver genes were found in all or a subset of a tumor and thus whether it was an early or late event in tumor evolution. It was concluded that most driver genes occurred as an early event. The genetic landscape of driverness and clonality in driver genes was drawn out in this study to unravel intratumor genetic heterogeneity and to further understand tumor evolution. Bachelor of Science in Biological Sciences 2015-12-01T02:47:52Z 2015-12-01T02:47:52Z 2015 2015 Final Year Project (FYP) http://hdl.handle.net/10356/65645 en Nanyang Technological University 35 p. application/pdf
spellingShingle DRNTU::Science::Biological sciences
Ng, Ming Hwee
Unravelling genetic heterogeneity of hepatocellular carcinoma with driver genes and subclones
title Unravelling genetic heterogeneity of hepatocellular carcinoma with driver genes and subclones
title_full Unravelling genetic heterogeneity of hepatocellular carcinoma with driver genes and subclones
title_fullStr Unravelling genetic heterogeneity of hepatocellular carcinoma with driver genes and subclones
title_full_unstemmed Unravelling genetic heterogeneity of hepatocellular carcinoma with driver genes and subclones
title_short Unravelling genetic heterogeneity of hepatocellular carcinoma with driver genes and subclones
title_sort unravelling genetic heterogeneity of hepatocellular carcinoma with driver genes and subclones
topic DRNTU::Science::Biological sciences
url http://hdl.handle.net/10356/65645
work_keys_str_mv AT ngminghwee unravellinggeneticheterogeneityofhepatocellularcarcinomawithdrivergenesandsubclones