TY  - JOUR
A1  - Mehmood, Rashid
A1  - Alsaleh, Alanoud
A1  - Want, Muzamil Y.
A1  - Ahmad, Ijaz
A1  - Siraj, Sami
A1  - Ishtiaq, Muhammad
A1  - Alshehri, Faizah A.
A1  - Naseem, Muhammad
A1  - Yasuhara, Noriko
T1  - Integrative molecular analysis of DNA methylation dynamics unveils molecules with prognostic potential in breast cancer
JF  - BioMedInformatics
N2  - DNA methylation acts as a major epigenetic modification in mammals, characterized by the transfer of a methyl group to a cytosine. DNA methylation plays a pivotal role in regulating normal development, and misregulation in cells leads to an abnormal phenotype as is seen in several cancers. Any mutations or expression anomalies of genes encoding regulators of DNA methylation may lead to abnormal expression of critical molecules. A comprehensive genomic study encompassing all the genes related to DNA methylation regulation in relation to breast cancer is lacking. We used genomic and transcriptomic datasets from the Cancer Genome Atlas (TGCA) Pan-Cancer Atlas, Genotype-Tissue Expression (GTEx) and microarray platforms and conducted in silico analysis of all the genes related to DNA methylation with respect to writing, reading and erasing this epigenetic mark. Analysis of mutations was conducted using cBioportal, while Xena and KMPlot were utilized for expression changes and patient survival, respectively. Our study identified multiple mutations in the genes encoding regulators of DNA methylation. The expression profiling of these showed significant differences between normal and disease tissues. Moreover, deregulated expression of some of the genes, namely DNMT3B, MBD1, MBD6, BAZ2B, ZBTB38, KLF4, TET2 and TDG, was correlated with patient prognosis. The current study, to our best knowledge, is the first to provide a comprehensive molecular and genetic profile of DNA methylation machinery genes in breast cancer and identifies DNA methylation machinery as an important determinant of the disease progression. The findings of this study will advance our understanding of the etiology of the disease and may serve to identify alternative targets for novel therapeutic strategies in cancer.
KW  - DNA methylation
KW  - epigenetic modification
KW  - breast cancer
KW  - genomics
KW  - in silico analysis
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321171
SN  - 2673-7426
VL  - 3
IS  - 2
SP  - 434
EP  - 445
ER  - 
TY  - JOUR
A1  - Sendell-Price, Ashley T.
A1  - Tulenko, Frank J.
A1  - Pettersson, Mats
A1  - Kang, Du
A1  - Montandon, Margo
A1  - Winkler, Sylke
A1  - Kulb, Kathleen
A1  - Naylor, Gavin P.
A1  - Phillippy, Adam
A1  - Fedrigo, Olivier
A1  - Mountcastle, Jacquelyn
A1  - Balacco, Jennifer R.
A1  - Dutra, Amalia
A1  - Dale, Rebecca E.
A1  - Haase, Bettina
A1  - Jarvis, Erich D.
A1  - Myers, Gene
A1  - Burgess, Shawn M.
A1  - Currie, Peter D.
A1  - Andersson, Leif
A1  - Schartl, Manfred
T1  - Low mutation rate in epaulette sharks is consistent with a slow rate of evolution in sharks
JF  - Nature Communications
N2  - Sharks occupy diverse ecological niches and play critical roles in marine ecosystems, often acting as apex predators. They are considered a slow-evolving lineage and have been suggested to exhibit exceptionally low cancer rates. These two features could be explained by a low nuclear mutation rate. Here, we provide a direct estimate of the nuclear mutation rate in the epaulette shark (Hemiscyllium ocellatum). We generate a high-quality reference genome, and resequence the whole genomes of parents and nine offspring to detect de novo mutations. Using stringent criteria, we estimate a mutation rate of 7×10\(^{−10}\) per base pair, per generation. This represents one of the lowest directly estimated mutation rates for any vertebrate clade, indicating that this basal vertebrate group is indeed a slowly evolving lineage whose ability to restore genetic diversity following a sustained population bottleneck may be hampered by a low mutation rate.
KW  - evolutionary genetics
KW  - genomics
KW  - molecular evolution
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357827
VL  - 14
ER  -