scholarly journals Tumors widely express hundreds of embryonic germline genes

2020 ◽  
Author(s):  
Jan Willem Bruggeman ◽  
Naoko Irie ◽  
Paul Lodder ◽  
Ans M.M. van Pelt ◽  
Jan Koster ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Germ Cells ◽  
Expression Profiles ◽  
Primordial Germ Cells ◽  
Cell Cancer ◽  
Tumor Development ◽  
Gene Expression Profiles ◽  
Cancer Genes ◽  
Germline Development ◽  
Tumor Types

AbstractWe have recently described a class of 756 genes that are widely expressed in cancer, while normally restricted to adult germ cells, referred to as germ cell cancer genes (GC-genes). We hypothesized that carcinogenesis involves reactivation of biomolecular processes and regulatory mechanisms that, under normal circumstances, are restricted to germline development. This would imply that cancer cells share gene expression profiles with primordial germ cells (PGCs). We therefore compared the transcriptomes of human PGCs (hPGCs) and PGC-like cells (PGCLCs) with 17 382 samples from 54 healthy somatic tissues (GTEx) and 11 003 samples from 33 tumor types (TCGA), and identified 672 GC-genes, expanding the known GC-gene pool by 387 genes (51%). Because GC-genes specific to the embryonic germline are not expressed in any adult tissue, targeting these in cancer treatment may result in fewer side effects than targeting conventional cancer/testis (CT) or GC-genes and may preserve fertility. We anticipate that our extended GC-dataset enables improved understanding of tumor development and may provide multiple novel targets for cancer treatment development.

scholarly journals Tumors Widely Express Hundreds of Embryonic Germline Genes

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3812
Author(s):  
Jan Willem Bruggeman ◽  
Naoko Irie ◽  
Paul Lodder ◽  
Ans M. M. van Pelt ◽  
Jan Koster ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Treatment ◽  
Germ Cells ◽  
Expression Profiles ◽  
Cell Cancer ◽  
Cancer Genes ◽  
Germline Development ◽  
Multiple Tumor ◽  
Tumor Types ◽  
Gc Gene

We have recently described a class of 756 genes that are widely expressed in cancers, but are normally restricted to adult germ cells, referred to as germ cell cancer genes (GC genes). We hypothesized that carcinogenesis involves the reactivation of biomolecular processes and regulatory mechanisms that, under normal circumstances, are restricted to germline development. This would imply that cancer cells share gene expression profiles with primordial germ cells (PGCs). We therefore compared the transcriptomes of human PGCs (hPGCs) and PGC-like cells (PGCLCs) with 17,382 samples from 54 healthy somatic tissues (GTEx) and 11,003 samples from 33 tumor types (TCGA), and identified 672 GC genes, expanding the known GC gene pool by 387 genes (51%). We found that GC genes are expressed in clusters that are often expressed in multiple tumor types. Moreover, the amount of GC gene expression correlates with poor survival in patients with lung adenocarcinoma. As GC genes specific to the embryonic germline are not expressed in any adult tissue, targeting these in cancer treatment may result in fewer side effects than targeting conventional cancer/testis (CT) or GC genes and may preserve fertility. We anticipate that our extended GC dataset enables improved understanding of tumor development and may provide multiple novel targets for cancer treatment development.

scholarly journals YAP Regulates the Expression ofHoxa1andHoxc13in Mouse and Human Oral and Skin Epithelial Tissues

2015 ◽  
Vol 35 (8) ◽  
pp. 1449-1461 ◽  
Author(s):  
Ming Liu ◽  
Shuangyun Zhao ◽  
Qingjie Lin ◽  
Xiu-Ping Wang
Keyword(s):  
Cell Proliferation ◽  
Expression Profiles ◽  
Tumor Development ◽  
Gene Expression Profiles ◽  
Tooth Germ ◽  
Conditional Knockout ◽  
Hippo Signaling ◽  
Embryonic Mouse ◽  
Downstream Targets ◽  
Epithelial Tissues

Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues.Yapdeficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5)Yapconditional knockout andYAPtransgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR andin situhybridization. We found that YAP regulates the expression ofHoxa1andHoxc13in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested thatHoxa1andHoxc13are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulateHoxa1andHoxc13expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans.

scholarly journals The Mammalian Ovary from Genesis to Revelation

2009 ◽  
Vol 30 (6) ◽  
pp. 624-712 ◽  
Author(s):  
Mark A. Edson ◽  
Ankur K. Nagaraja ◽  
Martin M. Matzuk
Keyword(s):  
Germ Cells ◽  
Ovarian Function ◽  
Primordial Germ Cells ◽  
Bioactive Molecules ◽  
Sex Characteristics ◽  
Germline Development ◽  
Peptide Growth Factors ◽  
Development And Differentiation ◽  
Common Destiny ◽  
Female Germline

Abstract Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago.

scholarly journals Minimal residual disease in multiple myeloma: current status

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Hong Ding ◽  
Juan Xu ◽  
Zhimei Lin ◽  
Jingcao Huang ◽  
Fangfang Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Expression Profiles ◽  
Cell Cancer ◽  
Gene Expression Profiles ◽  
Current Status ◽  
Cytogenetic Aberration ◽  
The Status ◽  
Minimal Residual

AbstractMultiple myeloma (MM) is a treatable plasma cell cancer with no cure. Clinical evidence shows that the status of minimal residual disease (MRD) after treatment is an independent prognostic factor of MM. MRD indicates the depth of post-therapeutic remission. In this review article, we outlined the major clinical trials that have determined the prognostic value of MRD in MM. We also reviewed different methods that were used for MM MRD assessment. Most important, we reviewed our current understanding of MM MRD biology. MRD studies strongly indicate that MRD is not a uniform declination of whole MM tumor population. Rather, MM MRD exhibits unique signatures of cytogenetic aberration and gene expression profiles, unlike those of MM cells before therapy. Diagnostic high-risk MM and low-risk MM exhibited a diversity of MRD features. Clonal evaluation may occur at the MRD stage in MM. The dynamics from the diagnostic MM to MRD correlate with the disease prognosis. Lastly, on the aspect of omics, we performed data-based analysis to address the biological features underlying the course of diagnostic-to-MRD MM. To summarize, the MRD stage of disease represents a critical step in MM pathogenesis and progression. Demonstration of MM MRD biology should help us to deal with the curative difficulties.

scholarly journals A truncated form of a transcription factor Mamo activates vasa in Drosophila embryos

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Shoichi Nakamura ◽  
Seiji Hira ◽  
Masato Fujiwara ◽  
Nasa Miyagata ◽  
Takuma Tsuji ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Transcriptional Activator ◽  
Transcriptional Regulators ◽  
Truncated Form ◽  
Germline Development ◽  
Finger Protein ◽  
Biochemical Studies ◽  
Drosophila Embryos

AbstractExpression of the vasa gene is associated with germline establishment. Therefore, identification of vasa activator(s) should provide insights into germline development. However, the genes sufficient for vasa activation remain unknown. Previously, we showed that the BTB/POZ-Zn-finger protein Mamo is necessary for vasa expression in Drosophila. Here, we show that the truncated Mamo lacking the BTB/POZ domain (MamoAF) is a potent vasa activator. Overexpression of MamoAF was sufficient to induce vasa expression in both primordial germ cells and brain. Indeed, Mamo mRNA encoding a truncated Mamo isoform, which is similar to MamoAF, was predominantly expressed in primordial germ cells. The results of our genetic and biochemical studies showed that MamoAF, together with CBP, epigenetically activates vasa expression. Furthermore, MamoAF and the germline transcriptional activator OvoB exhibited synergy in activating vasa transcription. We propose that a Mamo-mediated network of epigenetic and transcriptional regulators activates vasa expression.

Human Second Trimester Amniotic Fluid Cells are Able to Create Embryoid Body-Like Structures in Vitro and to Show Typical Expression Profiles of Embryonic and Primordial Germ Cells

2014 ◽  
Vol 23 (12) ◽  
pp. 1501-1515 ◽  
Author(s):  
Ivana Antonucci ◽  
Roberta Di Pietro ◽  
Melissa Alfonsi ◽  
Maria Antonietta Centurione ◽  
Lucia Centurione ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Germ Cells ◽  
Embryoid Body ◽  
Expression Profiles ◽  
Primordial Germ Cells ◽  
Second Trimester ◽  
Amniotic Fluid Cells

scholarly journals Identification of Lung-Cancer-Related Genes with the Shortest Path Approach in a Protein-Protein Interaction Network

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Bi-Qing Li ◽  
Jin You ◽  
Lei Chen ◽  
Jian Zhang ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Shortest Path ◽  
Protein Interaction ◽  
Expression Profiles ◽  
Shortest Paths ◽  
Gene Expression Profiles ◽  
Cancer Genes ◽  
Ppi Network ◽  
Protein Protein Interaction

Lung cancer is one of the leading causes of cancer mortality worldwide. The main types of lung cancer are small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC). In this work, a computational method was proposed for identifying lung-cancer-related genes with a shortest path approach in a protein-protein interaction (PPI) network. Based on the PPI data from STRING, a weighted PPI network was constructed. 54 NSCLC- and 84 SCLC-related genes were retrieved from associated KEGG pathways. Then the shortest paths between each pair of these 54 NSCLC genes and 84 SCLC genes were obtained with Dijkstra’s algorithm. Finally, all the genes on the shortest paths were extracted, and 25 and 38 shortest genes with a permutationPvalue less than 0.05 for NSCLC and SCLC were selected for further analysis. Some of the shortest path genes have been reported to be related to lung cancer. Intriguingly, the candidate genes we identified from the PPI network contained more cancer genes than those identified from the gene expression profiles. Furthermore, these genes possessed more functional similarity with the known cancer genes than those identified from the gene expression profiles. This study proved the efficiency of the proposed method and showed promising results.

scholarly journals Cancer stem cells: a new approach to tumor development

2015 ◽  
Vol 61 (1) ◽  
pp. 86-93 ◽  
Author(s):  
Natália Cristina Ciufa Kobayashi ◽  
Samuel Marcos Ribeiro de Noronha
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Cell Cancer ◽  
Tumor Development ◽  
New Approach ◽  
Tumor Types ◽  
Immunosuppressed Mice

Many theories have been proposed to explain the origins of cancer. Currently, evidences show that not every tumor cell is capable of initiating a tumor. Only a small part of the cancer cells, called cancer stem cells (CSCs), can generate a tumor identical to the original one, when removed from human tumors and transplanted into immunosuppressed mice. The name given to these cells comes from the resemblance to normal stem cells, except for the fact that their ability to divide is infinite. These cells are also affected by their microenvironment. Many of the signaling pathways, such as Wnt, Notch and Hedgehog, are altered in this tumoral subpopulation, which also contributes to abnormal proliferation. Researchers have found several markers for CSCs; however, much remains to be studied, or perhaps a universal marker does not even exist, since they vary among tumor types and even from patient to patient. It was also found that cancer stem cells are resistant to radiotherapy and chemotherapy. This may explain the re-emergence of the disease, since they are not completely eliminated and minimal amounts of CSCs can repopulate a tumor. Once the diagnosis in the early stages greatly increases the chances of curing cancer, identifying CSCs in tumors is a goal for the development of more effective treatments. The objective of this article is to discuss the origin of cancer according to the theory of stem cell cancer, as well as its markers and therapies used for treatment.

scholarly journals Discovering novel driver mutations from pan-cancer analysis of mutational and gene expression profiles

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242780
Author(s):  
Houriiyah Tegally ◽  
Kevin H. Kensler ◽  
Zahra Mungloo-Dilmohamud ◽  
Anisah W. Ghoorah ◽  
Timothy R. Rebbeck ◽  
...  
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Cancer Genomics ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Driver Mutations ◽  
Literature Mining ◽  
Cancer Genes ◽  
Multiple Cancer ◽  
Driver Genes

As the genomic profile across cancers varies from person to person, patient prognosis and treatment may differ based on the mutational signature of each tumour. Thus, it is critical to understand genomic drivers of cancer and identify potential mutational commonalities across tumors originating at diverse anatomical sites. Large-scale cancer genomics initiatives, such as TCGA, ICGC and GENIE have enabled the analysis of thousands of tumour genomes. Our goal was to identify new cancer-causing mutations that may be common across tumour sites using mutational and gene expression profiles. Genomic and transcriptomic data from breast, ovarian, and prostate cancers were aggregated and analysed using differential gene expression methods to identify the effect of specific mutations on the expression of multiple genes. Mutated genes associated with the most differentially expressed genes were considered to be novel candidates for driver mutations, and were validated through literature mining, pathway analysis and clinical data investigation. Our driver selection method successfully identified 116 probable novel cancer-causing genes, with 4 discovered in patients having no alterations in any known driver genes: MXRA5, OBSCN, RYR1, and TG. The candidate genes previously not officially classified as cancer-causing showed enrichment in cancer pathways and in cancer diseases. They also matched expectations pertaining to properties of cancer genes, for instance, showing larger gene and protein lengths, and having mutation patterns suggesting oncogenic or tumor suppressor properties. Our approach allows for the identification of novel putative driver genes that are common across cancer sites using an unbiased approach without any a priori knowledge on pathways or gene interactions and is therefore an agnostic approach to the identification of putative common driver genes acting at multiple cancer sites.

scholarly journals The Central Role of Cadherins in Gonad Development, Reproduction and Fertility

2020 ◽  
Author(s):  
Rafał P. Piprek ◽  
Malgorzata Kloc ◽  
Paulina Mizia ◽  
Jacek Z. KUBIAK
Keyword(s):  
Germ Cells ◽  
Reproductive Tract ◽  
Primordial Germ Cells ◽  
Somatic Cells ◽  
Gonad Development ◽  
Female Reproductive Tract ◽  
Future Research ◽  
Corpora Lutea ◽  
Germline Development

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, the E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells, (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, the N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood-testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes, and facilitate the capacitation of sperm in the female reproductive tract, and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins, however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and suggest the topics for future research.

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