Diverse modes of genomic alteration in hepatocellular carcinoma

Genome Biology
Suchit JhunjhunwalaZemin Zhang


Hepatocellular carcinoma (HCC) is a heterogeneous disease with high mortality rate. Recent genomic studies have identified TP53, AXIN1, and CTNNB1 as the most frequently mutated genes. Lower frequency mutations have been reported in ARID1A, ARID2 and JAK1. In addition, hepatitis B virus (HBV) integrations into the human genome have been associated with HCC. Here, we deep-sequence 42 HCC patients with a combination of whole genome, exome and transcriptome sequencing to identify the mutational landscape of HCC using a reasonably large discovery cohort. We find frequent mutations in TP53, CTNNB1 and AXIN1, and rare but likely functional mutations in BAP1 and IDH1. Besides frequent hepatitis B virus integrations at TERT, we identify translocations at the boundaries of TERT. A novel deletion is identified in CTNNB1 in a region that is heavily mutated in multiple cancers. We also find multiple high-allelic frequency mutations in the extracellular matrix protein LAMA2. Lower expression levels of LAMA2 correlate with a proliferative signature, and predict poor survival and higher chance of cancer recurrence in HCC patients, suggesting an important role of the extracellular matrix and cell adhesion in tumor progression of a subgroup of ...Continue Reading


Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
Mar 16, 2004·Science·Yardena SamuelsVictor E Velculescu
Dec 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jean J ZhaoThomas M Roberts
Feb 4, 2006·Parasitology·M Berriman
May 10, 2008·Bioinformatics·Pan DuSimon M Lin
Sep 6, 2008·Science·D Williams ParsonsKenneth W Kinzler
Feb 20, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sean F AltekruseMarsha E Reichman
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Dec 22, 2010·Journal of Cell Science·Virginia A SpencerMina J Bissell
May 12, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hiroshi TanakaYuko Aoki
Aug 2, 2011·Mutation Research·C M BusemanJ W Shay
Aug 16, 2011·Bioinformatics·Matthew K IyerChristopher A Maher
Oct 1, 2011·Liver International : Official Journal of the International Association for the Study of the Liver·Edmund Kwok-Kwan TungIrene Oi-Lin Ng
Dec 20, 2011·Nature Biotechnology·Joke ReumersJurgen Del-Favero
May 15, 2012·Bioinformatics·Christopher T SaundersR Keira Cheetham
May 29, 2012·Nature Genetics·Wing-Kin SungJohn M Luk
Aug 11, 2012·Science·Anwesha DeyVishva M Dixit
Sep 27, 2012·Nature Genetics·Zemin Zhang
Jan 26, 2013·Science·Franklin W HuangLevi A Garraway
Feb 8, 2013·Nature·Michael B BurnsReuben S Harris
Feb 21, 2013·Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine
Apr 4, 2013·Nature Reviews. Cancer·Michele CarboneGiovanni Gaudino
Jul 28, 2013·Nature Communications·João VinagrePaula Soares


Nov 15, 2015·Journal of Cellular Physiology·Justin T HuntingtonGustavo Leone
Nov 14, 2016·Carcinogenesis·Chinthalapally V RaoHiroshi Y Yamada
Jan 21, 2017·International Journal of Molecular Sciences·Ioannis D KyrochristosDimitrios H Roukos
Jul 25, 2018·Genes·Magdalena A BudzinskaThomas Tu
Jan 23, 2016·Journal of Virology·Takahisa KouwakiYoshiharu Matsuura
Dec 7, 2018·GigaScience·Weitai HuangCaroline G Lee
Jun 2, 2018·Panminerva Medica·Maja RužićLudovico Abenavoli
May 8, 2019·Microorganisms·Haripriya GuptaKi Tae Suk
Dec 5, 2019·Scientific Reports·David S GoerlitzChristopher A Loffredo
Nov 17, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yosuke OchiaiMasato Nagino
Feb 20, 2018·Frontiers in Genetics·Venkatesh KancherlaSalvatore Piscuoglio
Sep 19, 2017·Obesity·Kristin R PetersonAlyssa H Hasty
Apr 11, 2018·Frontiers in Medicine·Charlotte K Y NgSalvatore Piscuoglio
Jul 10, 2020·Cancer Research·Yutaka MidorikawaHiroyuki Aburatani

Datasets Mentioned


Methods Mentioned


Related Concepts

Lama2 protein, mouse
DNA Mutational Analysis
Hepatitis B
Dane Particle
Liver Carcinoma
Malignant Neoplasm of Liver
Variation (Genetics)
Survival Analysis
Genetic Heterogeneity

Related Feeds

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.