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Journal of Research and Reports on Genetics | Volume 3
November 07-08, 2019 | Melbourne, Australia
Molecular Biology and Genetic Engineering
International Conference on
C
hromosome mutations and rearrangements are some
of the hallmarks of human malignancies. Chromosomal
rearrangement is frequent in human cancers. One of the
consequences of chromosomal rearrangement is gene fusions
in the cancer genome. We have identified a panel of fusion
genes in aggressive prostate cancers. In the present study,
we found that these fusion genes are present in 7 different
types of human malignancies with variable frequencies.
Among them, CCNH-C5orf30 and TRMT11-GRIK2 gene
fusions were found in colon cancer, breast cancer, non-
small cell lung cancer, esophageal adenocarcinoma,
glioblastoma multiforme, ovarian cancer and liver cancer,
with frequencies ranging from 12.9% to 85%. In contrast,
four other gene fusions (mTOR-TP53BP1, TMEM135-
CCDC67, KDM4-AC011523.2 and LRRC59-FLJ60017) are
less frequent. Both TRMT11- GRIK2 and CCNH-C5orf30 are
also present in lymph node metastatic cancer samples from
the breast, colon and ovary. Thus, detecting these fusion
transcripts may have significant biological and clinical
implications in cancer patient management. Recently, we
developed a genome editing based technology to target
at the fusion gene breakpoints in human cancers through
insertion of suicide gene into the mutation sites. This
approach achieved high specificity in killing the cancer cells
and sparing the normal tissues from the collateral damages.
The treatment of mice xenografted with cancers that contain
the fusion genes achieved partial remission of the cancers.
As a result, the mutation targeting of human cancer genome
holds promise for the treatment of the disease.
Speaker Biography
Jianhua Luo has been studying molecular mechanisms of human
malignancies in the last 32 years. Currently, he is a Professor of Pathology
and Director of High Throughput Genome Center at University of
Pittsburgh. In the last 20 years, he has been largely focusing on the
genetic and molecular mechanism of human prostate and hepatocellular
carcinomas. He proposed prostate cancer field effect in 2002. He is one
of the pioneers in utilizing high throughput gene expression and genome
analyses to analyze field effects in prostate cancer and liver cancer. He is
also the first in using methylation array and whole genome methylation
sequencing to analyze prostate cancer. Recently, his group discovered
several novel fusion transcripts and their association with aggressive
prostate cancer. Subsequently, his group discovered that many of these
fusion genes are recurrent in many other types of human cancers.
e:
luoj@upmc.eduJianhua Luo
University of Pittsburgh, USA
Therapeutic targeting of genomic mutations in human cancers
Notes:
Jianhua Luo
, J Res Rep Genet 2019, Volume 3
DOI: 10.35841/2591-7986-C1-001